Agustin Jereza, Virgilio Gonzales, Miguel Sanson, Mrs. Natividad Villa-Albino, Felipe Ouano, Fructuoso Ramos, Hipolito Andrada, and Dr. Jose Mirasol felt the need to establish a private, non-sectarian educational institution that could offer high standards of instruction but within the reach of the average man in the community.

On May 14, 1927, these notable men and women founded the University of Southern Philippines, which was called Southern Institute at the time. The school offered a complete elementary course and the first two years of secondary education to 121 students at a rented building in Colon Street, Cebu City. In 1929, the school produced their first fifteen graduates.

Collegiate courses were opened in 1933. With the offering of complete collegiate courses in the Arts and Sciences, Education, Commerce, Law, the Southern Institute changed its name to The Southern College in 1937. Sadly, the Second World War razed the school buildings to the ground, with the exception of the façade of the Administration Building. The U.S. Army occupied the campus. The school was reconstructed and re-opened at Camputhaw (now Lahug) in 1945.

Having attained university status, the name Southern College was changed to University of Southern Philippines on July 8, 1949.

In 1959, USP was converted into a non-stock, non-profit foundation. On May 28, 1959, it was officially registered with the Securities and Exchange Commission (SEC) as a foundation.

In 1962, Don Agustin Jereza established the USP Lahug Campus, which is now the main campus of the University.

In 1977, the University celebrated its Golden Jubilee.

This 2022, the University of Southern Philippines Foundation celebrates 95 years as an academic institution and 73 years as a university staying true to its commitment to serve the nation by producing professionals in different fields of specialization. USPF continues to be a premiere educational institution that responds to the high demands of producing globally competitive graduates, upholding the values of professionalism, integrity, excellence, and social responsibility.