- Arts and literature
- Kevin Allison (1988) – comedic actor and writer, most notably a member of the comedy troupe The State
- David Bell (1988) – mystery author
- Matt Berninger (1989) – vocalist for indie rock band The National
- Andy Blankenbuehler (1988) – Broadway dancer and choreographer; Lucille Lortel Award winner; winner of the 2007 Drama Desk Award and 2008 Tony Award for Best Choreography in In the Heights
- Phil DeGreg (1972) – jazz pianist
- John Diehl (1968) – actor
- Thomas Hoobler (1960) – author and co-author of more than 90 published books, winner of the 2004 Edgar Award and the National Council for the Social Studies' 1997 Carter Godwin Woodson Award
- Joey Kern (1995) – movie actor, most notably in Cabin Fever (2002), Grind (2003), and Super Troopers
- Kevin Kern (1992) – Broadway performer in Les Misérables and Wicked
- John Knoepfle (c. 1940) – poet; author of Rivers Into Islands
- David Quammen (1966) – science writer
- Athletics
- Alex Albright (2006) – professional football linebacker, Dallas Cowboys
- Bob Arnzen (1965) – professional basketball and baseball player
- Jason Basil (1997) – minor league baseball player, 2000 ACC Baseball Tournament MVP
- Dana Bible (1972) – football coach, NC State Wolfpack
- Rocky Boiman (1998) – professional football player and Super Bowl XLI champion, Tennessee Titans
- Neal Brady (c. 1915) – pitcher for the New York Yankees and Cincinnati Reds
- Jayme Cramer (2001) – bronze medalist in swimming at the 2003 Pan American Games and silver medalist at the 2006 FINA Short Course World Championships
- Greg Frey (1986) – professional football player
- Clint Haslerig (1970) – professional football player
- Jim Herman (1996) – professional golfer
- Joe Hudepohl (1992) – gold medalist at the 1992 and 1996 Olympic Games; swimming world record holder
- Brad Jaeger (2003) – Indy Pro Series and Rolex Sports Car Series race car driver
- Melvin Johnson (1990) – professional football player, Tampa Bay Buccaneers and Kansas City Chiefs
- Charles Keating III – swimmer at the 1976 Olympic Games
- Luke Kuechly (2009) – professional football linebacker, Carolina Panthers
- Chris Mack (1988) – head coach, Xavier Musketeers men's basketball
- Lemar Marshall (1995) – professional football player, Cincinnati Bengals
- Mike Mathis – professional basketball referee
- Art Mergenthal (1939) – professional football player and 1945 NFL champion, Cleveland Rams
- Randy Newsom (2000) – minor league baseball pitcher, Akron Aeros
- Tom O'Brien (1966) – head football coach, NC State Wolfpack
- Dominic Randolph (2005) – Arena Football League quarterback
- Kyle Ransom (2003) – bronze medalist in swimming at the 2005 Summer Universiade
- George Ratterman (1944) – professional football player
- Shawn Rockey (1994) – professional soccer midfielder, Cincinnati Kings and Cincinnati Riverhawks
- Pat Ross (2001) – professional football player, Seattle Seahawks
- Greg Scruggs (2008) – professional football defensive end, Seattle Seahawks
- Chris Sexton (1989) – professional baseball player, Cincinnati Reds
- Steve Sollmann (2000) – minor league baseball infielder
- Bill Sweeney (c. 1904) – professional baseball player, Boston Doves
- Pat Todd (1998) – semifinalist in the men's lightweight coxless four rowing event at the 2004 Summer Olympics and the same event at the 2008 Summer Olympics
- Dod Wales (1995) – bronze medalist at the 1999 Pan Pacific Swimming Championships
- Chris Welsh (1973) – broadcaster and former professional baseball player
- Charles Wolf (1944) – former professional basketball coach
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- Clergy
- Most Rev. Henry K. Moeller (c. 1868) – Archbishop of Cincinnati
- Most Rev. Anthony John King Mussio (1920) – Bishop of Steubenville, Ohio
- Most Rev. Henry Richter (c. 1854) – Bishop of Grand Rapids, Michigan
- Education
- Francis M. Forster (1930) – neurologist and Dean of the Georgetown University School of Medicine; treated Dwight D. Eisenhower
- Joel M. Podolny – sociologist and Dean of the Yale School of Management
- Finance
- John F. Barrett – CEO of Western & Southern Financial Group
- Law and crime
- Michael Ryan Barrett (1969) – United States federal judge, Southern District of Ohio
- Joe Deters (1975) – Hamilton County Prosecuting Attorney
- Thomas Geoghegan (1967) – labor lawyer and author
- Charles H. Keating Jr. (1941) – lawyer, real estate developer, banker, and financier, convicted of fraud in the 1989 Savings and Loan scandal, after whom the Keating Five were named
- Joseph Peter Kinneary (1924) – United States federal judge, Southern District of Ohio
- Simon L. Leis, Jr. (1952) – Hamilton County Prosecutor (1971–1983), Common Pleas Judge (1983–1987), and Sheriff (1987–2012)
- Jeff Schare (1981) – detective, Cincinnati Police Department, featured on the A&E show The First 48
- Media
- James W. Faulkner (c. 1881) – newspaperman and political writer, "Dean of Ohio Correspondents"; founder of and first president of the Ohio Legislative Correspondents Association
- William J. Keating (1945) – U.S. House of Representatives (R–OH), 1971–1974, former publisher of The Cincinnati Enquirer and chairman of the board for Gannett Company and the Associated Press
- Joe Kernen (1974) – CNBC news anchor
- Greg Plageman (1987) – television screenwriter
- Gustave Reininger – television screenwriter
- Dave Straub (1997) – television producer
- Military
- John Herman Hoefker (1937) – World War II flying ace
- Politics
- Jeff Berding (1985) – Cincinnati City Councilman (D), 2005–2011
- Tom Brinkman (c. 1975) – Ohio State Representative (R–34), 2001–2008
- Jim Bunning (1949) – U.S. Senator (R–KY), 1999–2011; U.S. Representative (R–KY), 1987–1999; Hall of Fame professional baseball player
- John D. Carroll (1973) – Ohio State Representative (D–13), 1985
- John Cranley (1992) – Cincinnati City Councilman (D), 2000–2009
- Chip Cravaack (1977) – U.S. Representative (R–MN), 2011–2013
- Joseph L. DeCourcy, Jr. – Cincinnati City Councilman (R), 1957–1962; Hamilton County Commissioner (R), 1963–1970
- John J. Gilligan (1939) – Ohio Governor (D), 1971–1975; father of Health and Human Services Secretary Kathleen Sebelius
- Greg J. Holbrock (c. 1924) – U.S. Representative (D–OH), 1941–1943
- Eric Kearney (1981) – Ohio State Senator (D–9)
- Bill Kraus (1965) – gay rights and AIDS activist
- Robert Mecklenborg (1970) – Ohio State Representative (R–30), 2007–2011
- Peter Stautberg (1982) – Ohio State Representative (R–34)
- Jim Tarbell – Cincinnati City Councilman (C), 1998–2007
- Nick Vehr (1977) – Cincinnati City Councilman (R), 1994–1995
- Brad Wenstrup (1976) – U.S. Representative-elect (R–OH)
- Recipients of honorary diplomas
- Nick Clooney (1952) – television journalist, game show host, and politician
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