Construction of what is now the University's central administration building, South Building, took sixteen years before its completion in 1814. University President Joseph Caldwell toured the state by buggy to seek funds for completing the building. Additions to the building's original facade include a cupola in 1861, main doorway in 1897, and an Ionic portico on the South side in 1927.

From the South Building's second floor, President Caldwell conducted the first systematic observations of 'the haven know in the United States' between 1827 and 1831.

Today, the administrative offices of the Chancellor, the Provost, the College of Arts and Sciences, Minority Affairs, and Business and Finance are located here.

South Building has been the scene of numerous marches and sit-ins since the 1960s for causes ranging from civil rights to fair treatment of apparel workers in third-world countries.

The Office of Minority Affairs, which coordinates the University's minority recruitment programs and ensures that issues pertaining to minorities are included in campus decisions, is in South Building. The office employs many students in the administration of on-campus programs like Project Uplift and Pre-Orientation.