Benjamin Franklin (1706–1790) one of the more important figures in Pennsylvania and United States history. Although he was born in Boston, Massachusetts he came to Philadelphia as a young man. He founded the University of Pennsylvania in 1742, had the distinction of signing both the Declaration of Independence and the U.S. Constitution and is buried with his wife Deborah in Christ Church Cemetery in Philadelphia.

James Buchanan (1791–1868) was born and lived in Pennsylvania until his death. He was the 15th President of the United States and the only President from that state.

Rachel Carson (1907–1964) born near Springdale, was a pioneer environmentalist and author of Silent Spring

Winfield Scott Hancock (1824–1886) was born in Montgomery Square. He commanded Union troops during the American Civil War, most notably during the Battle of Gettysburg.

Smedley Butler (1880–1940) born in West Chester, Pennsylvania. Was a Major General in the U.S. Marine Corps and, at the time of his death, the most decorated Marine in U.S. history. Butler was awarded the Medal of Honor twice during his career

Pop artist Andy Warhol (1928–1987) was born Andrew Warhola in Pittsburgh. The Andy Warhol Museum is located in Pittsburgh's North Side, and he is buried in nearby Bethel Park.

General of the Army George C. Marshall (1880–1959) of Uniontown, led the United States Army as Chief of Staff during the Second World War. He later served as Secretary of State and authored the Marshall Plan.

Prince Demetrius Gallitzin (1770–1840) A Russian prince turned Roman Catholic missionary priest known as Apostle of the Alleghenies. He emigrated to the United States in 1792 and studied theology under Bishop John Carroll. In 1795, he became the first Catholic to receive all the orders of priesthood in the United States. In 1799 he used his own fortune to purchase 20,000 acres in Cambria County to form a Catholic community, the nucleus of the modern Roman Catholic Church west of the Allegheny Mountains. A prolific writer and apologist, he was declared a Servant of God in 2005, the first step on the road toward possible canonization.

Tom Ridge, The former Secretary of the U.S. Department of Homeland Security (1945-), was Governor of Pennsylvania between 1995 and 2003. Prior to that, he was a US Representative from Erie between 1982 and 1995.

Daniel Boone (1734–1820) was born in Birdsboro, Pennsylvania. He was the frontier explorer who was primarily responsible for establishing the Wilderness Road, the first viable route through the Cumberland Gap of the Appalachians into Kentucky. According to folklore, he named his Kentucky settlement, Boonesborough, in honor of his birthplace.