- Benjamin Lee Arnold (1862), American academic and the second president of Oregon State University
- George E. Barnett, professor of economics at Johns Hopkins University
- William Malone Baskervill, writer and professor of the English language and literature at Vanderbilt University
- Lambuth McGeehee Clarke, second president of Virginia Wesleyan College.
- John W. Craine Jr., president of SUNY Maritime College
- Richard Beale Davis, academic who specialised in the history of the Southern United States
- James F. Dowdell (1840), second president of the East Alabama College, now known as Auburn University, and representative from Alabama to the United States Congress
- Mary Virginia Gaver, librarian
- William Conrad Gibbons (1949), American historian and foreign policy expert
- Meta Glass, president of Sweet Briar College
- John Lesslie Hall, literary scholar at the College of William & Mary from 1888 to 1928
- M. Thomas Inge, Robert Emory Blackwell Professor of Humanities at Randolph–Macon College
- Samuel Lander, Methodist minister who founded what later became Lander University
- Henry Ludwell Moore, economist at Columbia University
- Christopher Morse, Christian theologian and professor of theology and ethics at Union Theological Seminary
- Holland Nimmons McTyeire (1844), American Bishop of the Methodist Episcopal Church, South and a co-founder of Vanderbilt University in Nashville, Tennessee
- Thomas G. Pullen, fifth president of the University of Baltimore
- James I. Robertson Jr., historian on the American Civil War and professor at Virginia Tech
- Holland Nimmons McTyeire, bishop of the Methodist Episcopal Church, South, and a co-founder of Vanderbilt University
- Andrew Sledd, first president of the University of Florida
- Wilbur Fisk Tillett, professor of systematic theology and dean of the theological faculty at Vanderbilt University
- Claude A. Swanson, U.S. Secretary of the Navy, U.S. Senator, and Governor of Virginia
- David W. Taylor (1881), rear admiral, U.S. Navy, and Chief Constructor of the Navy during World War I.
- E. Almer Ames Jr., member of the Virginia Senate
- Larry Preston Bryant, Jr. (1986), member of the Virginia House of Delegates who served as Secretary of Natural Resources under Governor Tim Kaine
- William Duval Cardwell, Virginia politician. He represented Hanover County in the Virginia House of Delegates, and served as that body's Speaker from 1906 until 1908
- Mildred Stafford Cherry, First Lady of North Carolina
- James Rives Childs (1912) was an American consular and diplomatic official for over thirty year
- David Clopton (1840), U.S. Congressman from Alabama, and associate justice of the Alabama Supreme Court
- Michael G. Comeau, former member of the Maryland House of Delegates
- James F. Dowdell (1840), second president of the East Alabama College, now known as Auburn University, from 1868 to 1870, and a representative from Alabama to the United States Congress
- Patrick H. Drewry (1896), U.S. Representative and state legislator from Virginia
- Randy Forbes (1974) U.S. Congressman from Virginia
- Porter Hardy Jr. (1922), U.S. Representative from Virginia
- William H. Hodges, Virginia Court of Appeals judge, Virginia Senate, and Virginia House of Delegates
- Joseph Chappell Hutcheson, Sr. (1861), Texas politician and a Democratic member of the Texas House of Representatives and the United States House of Representatives
- Thomas Jordan Jarvis (1861), 44th Governor of North Carolina from 1879 to 1885. Jarvis later served as a U.S. Senator
- James A. Jones, Virginia Senate
- Chris Jones (1980), member of the Virginia House of Delegates. In 2014, he was named chair of the House Appropriations Committee
- John J. Kindred, served five terms as U.S. Representative from New York
- Ira M. Lechner, Virginia House of Delegates
- John Letcher, Representative in the United States Congress, was the 34th Governor of Virginia during the American Civil War, and later served in the Virginia General Assembly
- Blanche Lincoln, United States Senator from Arkansas
- Drew Maloney, Assistant Secretary of the Treasury for Legislative Affairs
- David W. Marsden (1970), member of the Virginia Senate
- Walter Hines Page, journalist, U.S. Ambassador to the United Kingdom
- Margaret Bevans Ransone (1992), American politician elected to the Virginia House of Delegates in 2011
- James Williams Riddleberger (1924) U.S. Ambassador to Greece
- William McKendree Robbins (1850), U.S. Representative from North Carolina
- Margaret Ransonem, Virginia House of Delegates
- William M. Robbins, U.S. Representative from North Carolina
- Hugh Scott, Republican U.S. Congressman, U.S. Senator from Pennsylvania
- Matt Shaheen, Republican member of the Texas House of Representatives from Plano, Texas[2]
- Lemuel F. Smith, Justice of the Supreme Court of Virginia and Virginia House of Delegates
- Walter Leak Steele, U.S. Congressman
- Claude A. Swanson, U.S. Senator, Governor of Virginia, and U.S. Secretary of the Navy
- Walter Leak Steele, U.S. Congressman
- Joshua Soule Zimmerman (1892), member of the West Virginia House of Delegates.
- Michael Breed, professional golf instructor and host of The Golf Fix
- Christopher Chenery, owner/breeder of record for Thoroughbred horse racing's U.S. Triple Crown champion Secretariat
- Mike DeLotto, college football coach
- Milt Drewer, college football coach and athletic administrator
- Beth Dunkenberger (1988), head coach of the Virginia Tech women's basketball team
- Chris Gerlufsen, college basketball coach
- Paul Gilliford, Major League Baseball player
- Tim Landis, college football coach
- George Preston Marshall, founder and first owner of the NFL Washington Redskins
- Gregg Marshall (1985), head men's basketball coach at Wichita State
- Brian Partlow, head coach of the Arena Football League's Austin Wranglers
- Colin Selby, Major League Baseball player
- Chris Snyder, college football coach and athletics administrator
- Howard Stevens, professional football player
- Gary Strickler, athletic director at Boston University
- Syd Thrift, Major League Baseball player, scout, and general manager
- Frank Walker, Major League Baseball player