USF Sarasota-Manatee was established in 1975 as a regional campus of the University of South Florida and gained separate accreditation by the Southern Association of Colleges and Schools Commission on Colleges to award baccalaureate and master's degrees in June 2011.

After a campaign by Friends of Seagate for public acquisition this property had been brought into public ownership in 1991 by the state for the use of the sixteen bay front acres by Manatee County as a historical site and the remainder for research use by the environmental studies department of New College.

University students and community leaders participated on the team that created the design of the new facilities in a protracted charrette.

[clarification needed] The campus consists of two major buildings: In 2010 the campus became the home of a new facility for the radio and television networks of the university, WUSF (FM), WSMR (FM), and WUSF-TV that are part of the public broadcasting network.

On Aug. 19, 2024, USF Sarasota-Manatee opened its new Campus Student Center and Atala Residence Hall.