Historically, as of 1600, the tribes living in Pennsylvania were the Algonquian Lenape (also Delaware), the Iroquoian Susquehannock, and Petun (also Tionontati, Kentatentonga, Tobacco, Wenro) and the presumably Siouan Monongahela Culture, who may have been the same as a little known tribe called the Calicua, or Cali. Other tribes who entered the region during the colonial era were the Trockwae, Tutelo, Saponi, Shawnee, Nanticoke, Conoy Piscataway, Iroquois Confederacy—likely among others.

Other tribes, like the Erie, may have once held land in Pennsylvania, but no longer did so by the year 1600.

Both the Dutch and the English claimed both sides of the Delaware River as part of their colonial lands in America. The Dutch were the first to take possession.

By June 3, 1631, the Dutch had begun settling the Delmarva Peninsula by establishing the Zwaanendael Colony on the site of present-day Lewes, Delaware. In 1638, Sweden established the New Sweden Colony, in the region of Fort Christina, on the site of present-day Wilmington, Delaware. New Sweden claimed and, for the most part, controlled the lower Delaware River region (parts of present-day Delaware, New Jersey, and Pennsylvania) but settled few colonists there.

On March 12, 1664, King Charles II of England gave James, Duke of York a grant that incorporated all lands included in the original Virginia Company of Plymouth Grant plus other lands. This grant was in conflict with the Dutch claim for New Netherland, which included parts of today's Pennsylvania.

On June 24, 1664, the Duke of York sold the portion of his large grant that included present-day New Jersey to John Berkeley and George Carteret for a proprietary colony. The land was not yet in British possession, but the sale boxed in the portion of New Netherland on the West side of the Delaware River. The British conquest of New Netherland began on August 29, 1664, when New Amsterdam was coerced to surrender while facing cannons on British ships in New York Harbor. This conquest continued, and was completed in October 1664, when the British captured Fort Casimir in what today is New Castle, Delaware.

The Peace of Breda between England, France and the Netherlands confirmed the English conquest on July 21, 1667, although there were temporary reversions.

On September 12, 1672, during the Third Anglo-Dutch War, the Dutch re-conquered New York Colony/New Amsterdam, establishing three County Courts, which went on to become original Counties in present-day Delaware and Pennsylvania. The one that later transferred to Pennsylvania was Upland. This was partially reversed on February 9, 1674, when the Treaty of Westminster ended the Third Anglo-Dutch War, and reverted all political situations to the status quo ante bellum. The British retained the Dutch Counties with their Dutch names. By June 11, 1674, New York reasserted control over the outlying colonies, including Upland, but the names started to be changed to British names by November 11, 1674. Upland was partitioned on November 12, 1674, producing the general outline of the current border between Pennsylvania and Delaware.

On February 28, 1681, Charles II granted a land charter to William Penn to repay a debt of £16,000 (around £2,100,000 in 2008, adjusting for retail inflation) owed to William's father, Admiral William Penn. This was one of the largest land grants to an individual in history. The King named it Pennsylvania (literally "Penn's Woods") in honor of Admiral Penn; the Admiral's son who proposed that the land be called New Wales and then, after objections, Sylvania (from the Latin silva: "forest, woods"), was embarrassed at the change from the latter proposed form, fearing that people would think he had named it after himself, but King Charles would not rename the grant. Penn established a government with two innovations that were much copied in the New World: the county commission and freedom of religious conviction.

What had been Upland on what became the Pennsylvania side of the Pennsylvania-Delaware Border was renamed as Chester County when Pennsylvania instituted their colonial governments on March 4, 1681. The Quaker leader William Penn had signed a peace treaty with Tammany, leader of the Delaware tribe, beginning a long period of friendly relations between the Quakers and the Indians. Additional treaties between Quakers and other tribes followed. The treaty of William Penn was never violated.

Between 1730 and when it was shut down by Parliament with the Currency Act of 1764, the Pennsylvania Colony made its own paper money to account for the shortage of actual gold and silver. The paper money was called Colonial Scrip. The Colony issued "bills of credit", which were as good as gold or silver coins because of their legal tender status. Since they were issued by the government and not a banking institution, it was an interest-free proposition, largely defraying the expense of the government and therefore taxation of the people. It also promoted general employment and prosperity, since the Government used discretion and did not issue too much to inflate the currency. Benjamin Franklin had a hand in creating this currency, of which he said its utility was never to be disputed, and it also met with the "cautious approval" of Adam Smith.

James Smith wrote that in 1763, "the Indians again commenced hostilities, and were busily engaged in killing and scalping the frontier inhabitants in various parts of Pennsylvania." Further, "This state was then a Quaker government, and at the first of this war the frontiers received no assistance from the state." The ensuing hostilities became known as Pontiac's War.

After the Stamp Act Congress of 1765, Delegate John Dickinson of Philadelphia wrote the Declaration of Rights and Grievances. The Congress was the first meeting of the Thirteen Colonies, called at the request of the Massachusetts Assembly, but only nine colonies sent delegates. Dickinson then wrote Letters from a Farmer in Pennsylvania, To the Inhabitants of the British Colonies, which were published in the Pennsylvania Chronicle between December 2, 1767, and February 15, 1768.

When the Founding Fathers of the United States convened in Philadelphia in 1774, 12 colonies sent representatives to the First Continental Congress. The Second Continental Congress, which also met in Philadelphia (in May 1775), drew up and signed the Declaration of Independence in Philadelphia, but when that city was captured by the British, the Continental Congress escaped westward, meeting at the Lancaster courthouse on Saturday, September 27, 1777, and then to York. There they and its primary author, John Dickinson, drew up the Articles of Confederation that formed 13 independent States into a new union. Later, the Constitution was written, and Philadelphia was once again chosen to be cradle to the new American Union. The Constitution was drafted and signed at the Pennsylvania State House, now known as Independence Hall, and the same building where the Declaration of Independence was signed.

Pennsylvania became the first large state, and the second state to ratify the U.S. Constitution on December 12, 1787, five days after Delaware became the first. At the time it was the most ethnically and religiously diverse of the thirteen States. Because one-third of Pennsylvania's population spoke German, the Constitution was presented in German to include those citizens in the discussion. Reverend Frederick Muhlenberg acted as the chairman of the state's ratifying convention.

Dickinson College of Carlisle was the first college founded after the States united. Established in 1773, the college was ratified five days after the Treaty of Paris on September 9, 1783. The school was founded by Benjamin Rush and named after John Dickinson.

For half a century, the Commonwealth's General Assembly (legislature) met at various places in the general Philadelphia area before starting to meet regularly in Independence Hall in Philadelphia for 63 years. But it needed a more central location, as for example the Paxton Boys massacres of 1763 had made the legislature aware. So, in 1799 the General Assembly moved to the Lancaster Courthouse, and finally in 1812 to Harrisburg.

During the American Civil War, the Battle of Gettysburg was fought in the south central region of the state. The General Assembly met in the old Dauphin County Court House until December 1821, when the Federal-style "Hills Capitol" (named for its builder, Stephen Hills, a Lancaster architect) was constructed on a hilltop land grant of four acres set aside for a seat of state government by the prescient, entrepreneurial son and namesake of John Harris, Sr., a Yorkshire native who had founded a trading post in 1705 and ferry (1733) on the east shore of the Susquehanna River. The Hills Capitol burned down on February 2, 1897, during a heavy snowstorm, presumably because of a faulty flue.
The General Assembly met at Grace Methodist Church on State Street (still standing) until a new capitol could be built. Following an architectural selection contest that many alleged had been "rigged", Chicago architect Henry Ives Cobb was charged with designing and building a replacement building; however, the legislature had little money to allocate to the project, and a roughly finished, somewhat industrial building (the Cobb Capitol) was completed. The General Assembly refused to occupy the building. Political and popular indignation in 1901 prompted a second contest that was restricted to Pennsylvania architects, and Joseph Miller Huston of Philadelphia was chosen to design the present Pennsylvania State Capitol that incorporated Cobb's building into magnificent public work finished and dedicated in 1907.

The new state Capitol drew rave reviews. Its dome was inspired by the domes of St. Peter's Basilica in Rome and the United States Capitol. President Theodore Roosevelt called it "the most beautiful state Capital in the nation" and said, "It's the handsomest building I ever saw" at the dedication. In 1989, The New York Times praised it as "grand, even awesome at moments, but it is also a working building, accessible to citizens ... a building that connects with the reality of daily life".

James Buchanan, of Franklin County, the only bachelor president of the United States (1857–1861), was the first president to be born in Pennsylvania. The Battle of Gettysburg—the major turning point of the Civil War—took place near Gettysburg. An estimated 350,000 Pennsylvanians served in the Union Army forces including 8,600 African American military volunteers.

Pennsylvania was also the home of the first commercially drilled oil well. In 1859, near Titusville, Pennsylvania, Edwin Drake successfully drilled the well, which led to the first major oil boom in United States history.

At the beginning of the 20th century, Pennsylvania's economy centered on steel production, logging, coal mining, textile production and other forms of industrial manufacturing. A surge in immigration to the U.S. during the late 19th and early 20th centuries provided a steady flow of cheap labor for these industries, which often employed children and people who could not speak English.

In 1923, President Calvin Coolidge established the Allegheny National Forest under the authority of the Weeks Act of 1911. The forest is located in the northwest part of the state in Elk, Forest, McKean, and Warren Counties for the purposes of timber production and watershed protection in the Allegheny River basin. The Allegheny is the state's only national forest.

The Three Mile Island accident was the most significant nuclear accident in U.S. commercial nuclear power plant history.

United Airlines Flight 93 crashed into a field near Shanksville during the September 11th attacks, killing 44.

Within the first half of 2003, the annual Tekko commences in Pittsburgh.

In October 2018, the Tree of Life – Or L'Simcha Congregation experienced the Pittsburgh synagogue shooting.

Pennsylvania is 170 miles (274 km) north to south and 283 miles (455 km) east to west. Of a total 46,055 square miles (119,282 km²), 44,817 square miles (116,075 km²) are land, 490 square miles (1,269 km²) are inland waters, and 749 square miles (1,940 km²) are waters in Lake Erie. It is the 33rd-largest state in the United States. Pennsylvania has 51 miles (82 km) of coastline along Lake Erie and 57 miles (92 km) of shoreline along the Delaware Estuary. Of the original Thirteen Colonies, Pennsylvania is the only state that does not border the Atlantic Ocean.

The boundaries of the state are the Mason–Dixon line (39°43' N) to the south, the Twelve-Mile Circle on the Pennsylvania-Delaware border, the Delaware River to the east, 80°31' W to the west and the 42° N to the north, except for a short segment on the western end, where a triangle extends north to Lake Erie.

Cities include Philadelphia, Reading, Lebanon and Lancaster in the southeast, Pittsburgh in the southwest, and the tri-cities of Allentown, Bethlehem, and Easton in the central east (known as the Lehigh Valley). The northeast includes the former anthracite coal mining cities of Scranton, Wilkes-Barre, Pittston, Nanticoke, and Hazleton. Erie is located in the northwest. State College serves the central region while Williamsport serves the commonwealth's north-central region as does Chambersburg in the south-central region, with York, Carlisle, and the state capital Harrisburg on the Susquehanna River in the east-central region of the Commonwealth and Altoona and Johnstown in the west-central region.

The state has five geographical regions, namely the Allegheny Plateau, Ridge and Valley, Atlantic Coastal Plain, Piedmont, and the Erie Plain.

Pennsylvania's diverse topography also produces a variety of climates, though the entire state experiences cold winters and humid summers. Straddling two major zones, the majority of the state, except for the southeastern corner, has a humid continental climate (Köppen climate classification Dfb). The southern portion of the state has a humid subtropical climate. The largest city, Philadelphia, has a humid subtropical climate (Köppen Cfa).

Summers are generally hot and humid. Moving toward the mountainous interior of the state, the winter climate becomes colder, the number of cloudy days increases, and snowfall amounts are greater. Western areas of the state, particularly locations near Lake Erie, can receive over 100 inches (250 cm) of snowfall annually, and the entire state receives plentiful precipitation throughout the year. The state may be subject to severe weather from spring through summer into autumn. Tornadoes occur annually in the state, sometimes in large numbers, such as 30 recorded tornadoes in 2011; generally speaking, these tornadoes do not cause significant damage.

Pennsylvania is divided into 67 counties. Counties are further subdivided into municipalities that are either incorporated as cities, boroughs, or townships. One county, Philadelphia County, is coterminous with the city of Philadelphia after it was consolidated in 1854. The most populous county in Pennsylvania is Philadelphia, while the least populous is Cameron (4,547).

There are a total of 56 cities in Pennsylvania, which are classified, by population, as either first-, second-, or third-class cities. Philadelphia, Pennsylvania's largest city, has a population of 1.6 million and is the state's only first-class city. Pittsburgh (303,000) and Scranton (76,000) are second-class and second-class 'A' cities, respectively.

The rest of the cities, like the third and fourth-largest—Allentown (126,000) and Reading (95,000)—to the smallest—Parker with a population of only 820—are third-class cities. First- and second-class cities are governed by a "strong mayor" form of mayor–council government, whereas third-class cities are governed by either a "weak mayor" form of government or a council–manager government.

Boroughs are generally smaller than cities, with most Pennsylvania cities having been incorporated as a borough before being incorporated as a city. There are 958 boroughs in Pennsylvania, all of which are governed by the "weak mayor" form of mayor-council government. The largest borough in Pennsylvania is State College (40,501) and the smallest is Centralia.

Townships are the third type of municipality in Pennsylvania and are classified as either first-class or second-class townships. There are 1,454 second-class townships and 93 first-class townships. Second-class townships can become first-class townships if they have a population density greater than 300 inhabitants per square mile (120/km²) and a referendum is passed supporting the change. Pennsylvania's largest township is Upper Darby Township (85,681), and the smallest is East Keating Township.

There is one exception to the types of municipalities in Pennsylvania: Bloomsburg was incorporated as a town in 1870 and is, officially, the only town in the state. In 1975, McCandless Township adopted a home-rule charter under the name of "Town of McCandless", but is, legally, still a first-class township.

The total of 56 cities, 958 boroughs, 93 first-class townships, 1,454 second-class townships, and one town (Bloomsburg) is 2,562 municipalities.

As of the 2020 U.S. census, Pennsylvania had a population of 13,011,844, up from 12,702,379 in 2010. In 2019, net migration to other states resulted in a decrease of 27,718, and immigration from other countries resulted in an increase of 127,007. Net migration to the Commonwealth was 98,289. Migration of native Pennsylvanians resulted in a decrease of 100,000 people. From 2008 to 2012, 5.8% of the population was foreign-born.

Of the people residing in Pennsylvania, 74.5% were born in Pennsylvania, 18.4% were born in a different U.S. state, 1.5% were born in Puerto Rico, U.S. Island areas, or born abroad to American parent(s), and 5.6% were foreign born. Foreign-born Pennsylvanians are largely from Asia (36.0%), Europe (35.9%), and Latin America (30.6%), with the remainder from Africa (5%), North America (3.1%), and Oceania (0.4%).

The largest ancestry groups are listed below, expressed as a percentage of total people who responded with a particular ancestry for the 2010 census:

Pennsylvania's Hispanic or Latino American population grew by 82.6% between 2000 and 2010, making it one of the largest increases in a state's Hispanic population. The significant growth of the Hispanic or Latino population is due to migration to the state mainly from Puerto Rico, which is a U.S. territory, but to a lesser extent immigration from countries such as the Dominican Republic, Mexico, and various Central and South American nations, as well as from the wave of Hispanic and Latinos leaving New York and New Jersey for safer and more affordable living. The Asian population swelled by almost 60%, which was fueled by Indian, Vietnamese, and Chinese immigration, as well the many Asian transplants moving to Philadelphia from New York. The rapid growth of this community has given Pennsylvania one of the largest Asian populations in the nation by numerical values. The Black and African American population grew by 13%, which was the largest increase in that population amongst the state's peers (New York, New Jersey, Ohio, Illinois, and Michigan). Twelve other states saw decreases in their non-Hispanic white populations. The state has a high in-migration of black and Hispanic people from other nearby states, with eastern and south-central portions of the state seeing the bulk of the increases.

The majority of Hispanic or Latino Americans in Pennsylvania are of Puerto Rican descent, having one of the largest and fastest-growing Puerto Rican populations in the country. Most of the remaining Hispanic or Latino population is made up of Mexicans and Dominicans. Most Hispanic or Latinos are concentrated in Philadelphia, Lehigh Valley and South Central Pennsylvania. Pennsylvania's reported population of Hispanics or Latino Americans, especially among the Black race, has markedly increased in recent years. The Hispanic or Latino population is greatest in Bethlehem, Allentown, Reading, Lancaster, York, and around Philadelphia. It is not clear how much of this change reflects a changing population and how much reflects increased willingness to self-identify minority status. As of 2010, it is estimated that about 85% of all Hispanics or Latino Americans in Pennsylvania live within a 150-mile (240 km) radius of Philadelphia, with about 20% living within the city itself.

Of the black population, the vast majority in the state are African American, being descendants of African slaves brought to the U.S. south during the colonial era. There are also a growing number of blacks of West Indian, recent African, and Hispanic or Latino origins. Most blacks live in the Philadelphia area, Pittsburgh, and South Central Pennsylvania. Non-Hispanic whites make up the majority of Pennsylvania; they are mostly descended from German, Irish, Scottish, Welsh, Italian, and English immigrants. Rural portions of South Central Pennsylvania are famous nationwide for their notable Amish communities. The Wyoming Valley, consisting of Scranton and Wilkes-Barre, has the highest percentage of white residents of any metropolitan area (with a population of 500,000 or above) in the U.S., with 96.2% of its population claiming to be white with no Hispanic background.

The center of population of Pennsylvania is located in Perry County, in the borough of Duncannon.

The state had the fourth-highest proportion of elderly (65+) citizens in 2010—15.4%, as compared to 13.0% nationwide. According to U.S. Census Bureau estimates, the state's poverty rate was 12.5% in 2017, compared to 13.4% for the United States as a whole.

Note: Births in table do not add up because Hispanics are counted both by their ethnicity and by their race, giving a higher overall number.

As of 2010, 90.2% (10,710,239) of Pennsylvania residents age 5 and older spoke English at home as a primary language, while 4.1% (486,058) spoke Spanish, 0.8% (103,502) German (which includes Pennsylvania Dutch) and 0.5% (56,052) Chinese (which includes Mandarin) of the population over the age of five. In total, 9.9% (1,170,628) of Pennsylvania's population age 5 and older spoke a mother language other than English.

Pennsylvania German is often—even though misleadingly—called "Pennsylvania Dutch". The term Dutch used to mean "German" (including the Netherlands), before the Latin name for them replaced it (but stuck with the Netherlands). When referring to the language spoken by the Pennsylvania Dutch people (Pennsylvania German) it means "German" or "Teutonic" rather than "Netherlander". Germans, in their own language, call themselves "Deutsch", (Pennsylvania German: "Deitsch"). The Pennsylvania German language is a descendant of German, in the West Central German dialect family. It is closest to Palatine German. Pennsylvania German is still very vigorous as a first language among Old Order Amish and Old Order Mennonites (principally in the Lancaster County area), whereas it is almost extinct as an everyday language outside the plain communities, though a few words have passed into English usage.

Of all the colonies, only Rhode Island had religious freedom as secure as in Pennsylvania. Voltaire, writing of William Penn in 1733, observed: "The new sovereign also enacted several wise and wholesome laws for his colony, which have remained invariably the same to this day. The chief is, to ill-treat no person on account of religion, and to consider as brethren all those who believe in one God." One result of this uncommon freedom was a wide religious diversity, which continues to the present.

Pennsylvania's population in 2010 was 12,702,379; of these, 6,838,440 (53.8%) were estimated to belong to some sort of organized religion. According to the Association of Religion Data Archives (ARDA) at Pennsylvania State University, the largest religious bodies in Pennsylvania by adherents were the Roman Catholic Church with 3,503,028 adherents, the United Methodist Church with 591,734 members, and the Evangelical Lutheran Church in America with 501,974 members. Since 2014 among the religious population, 73% of the state was Christian per the Pew Research Center. In 2020, the Public Religion Research Institute estimated 68% of the population identified with Christianity. Among all surveys, the Roman Catholic Church remained the single-largest Christian denomination in the state.

Pennsylvania, especially in the west and in the Pittsburgh area, has one of the largest communities of Presbyterians in the nation, being the third highest by percentage of population and the largest outright in membership as Protestant Christians. The Presbyterian Church (USA), with about 250,000 members and 1,011 congregations, is the largest Presbyterian denomination while the Presbyterian Church in America is also significant, with 112 congregations and approximately 23,000 adherents; the EPC has around 50 congregations, as well as the ECO according to 2010 estimates. The fourth-largest Protestant denomination, the United Church of Christ, has 180,000 members and 627 congregations in the state. The American Baptist Churches USA (also referred to as the Northern Baptist Convention) is based in King of Prussia, Pennsylvania.

Pennsylvania was the center state of the German Reformed denomination from the 1700s. Bethlehem, Pennsylvania, is one of the headquarters of the Moravian Church in America. Pennsylvania also has a very large Amish population, second only to Ohio among the U.S. states. In the year 2000 there was a total Amish population of 47,860 in Pennsylvania and a further 146,416 Mennonites and 91,200 Brethren. The total Anabapist population including Bruderhof was 232,631, about two percent of the population. While Pennsylvania owes its existence to Quakers, and much of the historic character of the Commonwealth is ideologically rooted in the teachings of the Religious Society of Friends (as they are officially known), practicing Quakers are a small minority of about 10,000 adherents in 2010.