Affiliated with the United Methodist Church, it is one of ten historically black colleges and universities (HBCUs) founded before 1868 that are still operating.

One of the oldest colleges for African Americans in the United States, Rust was founded on November 24, 1866, by Northern missionaries with a group called the Freedman's Aid Society of the Methodist Episcopal Church.

[2] In 1892, to avoid confusion with Shaw University in Raleigh, North Carolina, the institution changed its name to Rust University—a tribute to Rev.

Richard S. Rust of Cincinnati, Ohio, a preacher, abolitionist, and the secretary of the Freedmen's Aid Society, who helped found the college.

Two historic markers honoring the Council of Federated Organizations and those involved in the 1964 Freedom Summer Project in Holly Springs were unveiled on campus in 2014.

For certain single sports, the Rust Bearcats softball team competed in the defunct D-III Great South Athletic Conference (GSAC) as an affiliate member from 2013–14 to 2014–15.