- William B. Allison – U.S. Senator from Iowa
- Ronnie Anderson (1997) – Former National Football League player
- Glenn Beckert – Former Major League Baseball player for the Chicago Cubs
- Ted Black – President of the Buffalo Sabres; former Vice President of the Pittsburgh Penguins (1999–2008)
- Ben Burtt – Academy Award winning sound designer
- Raymond Lysowski – World War II bombardier of 50 combat missions and Silver Life Master contract bridge player
- Robert J. Corbett, U.S. Representative for Pennsylvania (1939–1941, 1945–1971)
- Aylett R. Cotton, U.S. Representative for Iowa (1871–1875)
- George M. Davison – Inventor & CEO of Davison Associates, holds four patents
- Clarence Darrow – Noted American lawyer
- Bill Demchak – President of PNC Financial Services Group
- Valentino Achak Deng – Lost Boy of Darfur, and subject of the book What Is the What: The Autobiography of Valentino Achak Deng
- Rich Dohr – Music director and pianist for The Eagles and Don Henley
- Robert Dowling – Surgeon who performed the first fully implantable artificial heart implementation in a human patient
- Stan Drayton (1993) – National Football League assistant coach
- Budd Dwyer – Former Pennsylvania State Treasurer
- Morris P. Fiorina – Political scientist, leading scholar on voting behavior
- Beth Gylys (1986) – Professor at Georgia State University and award-winning poet
- Orville Nelson Hartshorn – founder of Mount Union College
- Daniel Brodhead Heiner – US Congressman for Pennsylvania (1893–1897)
- John M. Hillkirk II (1978) – Journalist, author and editor – Editor of USA Today (2009 – current)
- R. Keith Hillkirk (1968) – Chancellor of Penn State University, Berks College and Professor of Education
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- Gene Hong – TV writer, actor and producer
- Specs Howard – Founder of Specs Howard School of Media Arts
- Lloyd Lowndes, Jr. – 43rd Governor of Maryland (1896–1900), US Congressman (1873–1875)
- Benjamin F. Martin (1854) – US Congressman (1877–1881)
- Brooke McEldowney – Cartoonist, 9 Chickweed Lane
- Russ McKelvy – Former Major League Baseball player
- William McKinley – 25th President of the United States of America
- Richard Murphy (1971) – Pulitzer Prize-winning photographer
- Michelle Pawk – Actress (attended Allegheny for two years, 1980–1982)
- Trent Reznor (1983) – Musician (Nine Inch Nails)
- Barbara Robinson – author, The Best Christmas Pageant Ever (1972) and The Best School Year Ever (1994)
- Lloyd Segan - TV and Film Producer
- Raymond P. Shafer (1938) – Former Governor of Pennsylvania (1967–1971)
- Josh Sharpless (2003) – Relief pitcher for the Pittsburgh Pirates baseball team
- Edward Shanbrom (1947) – Pioneering hematologist and medical researcher
- Paul Siple (1932) – Antarctic explorer and the originator of the wind chill factor
- Alex Steffen (1990) – Environmental journalist
- Barry E. B. Swain Episcopal priest, opponent of women's ordination
- Ida M. Tarbell (1880) – Author, journalist, and muckraker. Published famous exposé on the Standard Oil Company.
- Mike Veon – Pennsylvania State Representative (1985–2006)
- Jeff Verszyla – Chief weather forecaster, KDKA-TV Pittsburgh
- James Villa (1958) - Former Canadian Football League player
- Erastus Wentworth (1850) – Methodist Episcopal minister
- Bradley Roland Will (1992) – Anarchist and journalist (1970–2006)
- Rob Wonderling – Pennsylvania State Senator (2003–2009)
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