In the summer of 1872, South College, a four-story dormitory building designed to accommodate 96 men in 24 rooms that housed four each, was constructed at a cost of $10,513.98. The architect was A. C. Bruce. The original plan had been to construct a three-story building at a cost of $10,000, but the nature of the soil required more excavation for the foundation than had been anticipated, and two large basement rooms resulted. The faculty voted on September 22, 1872, to allocate one of these two rooms to Lt. Thornburgh, the university commandant, for use as an armory. In December 1872 the faculty requested that President Humes maintain an on-campus office, and a room on the southeast corner of the first floor was set aside for the president’s use. The Cooperative Bookstore and the post office were given space in 1902. The building was extensively renovated in 1907, at which time the roofline was changed, porches were added, classrooms were enlarged, and the old lodging rooms eliminated.
In 1920 the general administrative offices of the university, including the President’s Office, were moved from Science Hall to South College, joining the bookstore and the post office. The university’s first cafeteria (under the direction of home economics professor and dietitian Lila Isles) was in the basement from 1922 until the opening of Sophronia Strong Cafeteria in 1925. In 1925 the former cafeteria was converted into meeting and lounge space for the campus YWCA. The first institutional bulletin board was placed outside South College in fall 1922.
In 1934 Acting President James D. Hoskins decided against razing South College, stating that it “is appropriate to keep a link with the past, and South College is worthy of that link.” Extensive improvements were made in 1935, with PWA/WPA funds, and the Department of Related Art moved into the building in 1936. Also in 1935 the old music room at the rear of the basement was converted into a studio room for the UT-WSM hook-up through which educational programs were sent to Nashville for broadcast. By 1947 radio operations, expanded for local broadcast, moved to the third floor; the staffs of the Orange and White and Volunteer moved into the basement, followed by use of the basement as the mailing facility for the Alumni Association and in 1965 a snack shop operated by a blind vendor under a program of the Tennessee Department of Rehabilitation Services for the Blind. In the 1950s the building was used by the Psychology Department.
With a state appropriation of $900,000, the building was fully renovated in 1987–88 for use as the headquarters of the Science Alliance and for aspects of its role as a Center of Excellence. The structural condition of the building required the installation of “earthquake bolts” like those seen in Charleston, South Carolina. The decorative iron gib plates and bolts on the exterior are attached to steel cables, and the system keeps the building structurally sound. In 2007 the Science Alliance offices moved, and the building was assigned to the Physics Department. In 2010, in order to allow the Arts and Sciences Advising Center to be fitted into the renovated Ayres Hall, a portion of the building was reassigned from Physics to Mathematics to provide offices for mathematics graduate teaching assistants.