After Hillsborough County High School moved out of the building on Highland Ave., Thomas Jefferson Junior High School was founded here in 1928. In 1939, due to the increasing high school population in the Tampa area, Thomas Jefferson High School was founded in the Old Hillsborough County High School building at 2704 N. Highland Avenue in the city's Tampa Heights neighborhood. Named after the third president of the United States, Thomas Jefferson, its first principal was D.W. Waters and its first class graduated in 1942.

By 1967, the school board decided that its location no longer met modern educational requirements and the first Jefferson High School was closed. Upon closure of the school, students were sent to neighboring schools to complete their education. The original Thomas Jefferson High School building still exists today as the D. W. Waters Career Center. Thomas Jefferson Archives

On August 27, 1973, the new Jefferson High School building was opened at its current location on West Cypress Street. Visit the Alumni Museum located at D. W. Waters Career Center, for the rich history of Jefferson High School.  The Jefferson High School Alumni Museum, Tampa (tampapix.com) 

Notable alumni include:

• Ferdie Pacheco (1944) Personal physician for Muhammad Ali
• Rick Casares (1950) AFL/NFL Football player
• Bob Marinez (1950) Former Tampa Mayor & Florida Governor
• Tonay La Russa (1962) Major League Baseball player/manager
• Joe Lala (1965) Musician & Actor
• Tony Zappone (1965) Author, photojournalist, broadcaster
• Fred McGriff (1981) Major League Baseball player
• Oscar  Smith (1981) NFL Football player
• Luis Gonzalez (1985) Major League Baseball player
• Tino Martinez (1985) Major League Baseball player
• Coleman Bell (1988) NFL Football player
• Torrance Small (1988) NFL Football player
• Kirby Dar Dar (1989) NFL Football player
• K. D. Willaims (1990) NFL Football player
• Keith Newman (1995) NFL Football player
• Reche Caldwell (1997) NFL Football player
• Tarence Kinsey (2002) NBA Basketball player
• Andre Caldwell (2003) NFL Football player
• Prechae Rodriguz (2003) CFL Football player
• Ramik Wilson (2011) NFL Football player
• Chris Moore (2011) NFL Football player
• Jimmy Herget (2012) Major League Baseball player