In the antebellum era, the Palmetto State generously supported the South Carolina College. The institution featured a cosmopolitan faculty, including such noted scholars as Europeans Francis Lieber and Thomas Cooper, as well as renowned American scholars John and Joseph LeConte. Offering a traditional classical curriculum, South Carolina College became one of the most influential colleges in the South before 1861, earning a reputation as the training ground for South Carolina's antebellum elite.

Then disaster struck. South Carolina's secession from the Union unleashed the devastation of civil war. The state and the South Carolina College paid dearly. The institution closed for want of students, and in the ensuing decades it struggled to regain the leading role in the region it had held during the antebellum era. State leaders revived the institution in 1866 with ambitious plans for a diverse university, but with a nearly empty state treasury, the institution failed to reach its former status.

As Reconstruction from the Civil War proceeded in South Carolina, the General Assembly chose the first African Americans to serve on the University's Board of Trustees in 1868, and in 1873 the first black students enrolled. While politically controversial, this development was an extraordinary opportunity for South Carolinians at a time when opportunities for higher education were rare. The University of South Carolina became the only southern state university to admit and grant degrees to African-American students during the Reconstruction era.

Following the end of Reconstruction in 1877, South Carolina's conservative leaders closed the University. They reopened it in 1880 as an all-white agricultural college, and over the next 25 years the institution became enmeshed in the political upheaval of late 19th-century South Carolina. Carolina went through several reorganizations in which the curriculum frequently changed and its status shifted from college to university and back again.

In 1906, the institution was rechartered for the final time as the University of South Carolina. In the early decades of the 20th century, Carolina made strides toward becoming a comprehensive university, and in 1917 became the first state-supported college or university in South Carolina to earn regional accreditation. The 1920s witnessed further progress and growth, with the introduction of new colleges and degree programs, including the doctorate.

The Great Depression temporarily stalled this progress, but the outbreak of World War II launched an era that transformed the University. Carolina hosted Naval training programs during the war, and enrollment more than doubled in the post-war era as veterans took advantage of the G.I. Bill. In the 1950s, the University began recruiting national-caliber faculty and extended its presence beyond Columbia with the establishment of campuses in communities across South Carolina.

In 1963 the University of South Carolina became the university of all the people of South Carolina. As the result of a federal court order, on September 11, Henrie D. Monteith, Robert Anderson, and James Solomon became the first of an increasing number of African-American students to enroll at the University in the 20th century. In the ensuing years, Carolina underwent explosive growth as the "baby boom" generation entered college. Enrollment stood at 5,660 in 1960, but by 1979 had reached nearly 26,000 students on the Columbia campus alone. To meet the needs of these students and South Carolina's changing economy, the University put new emphasis on research and introduced innovative degree programs as well as a number of new schools and colleges. Carolina had become a true research university.

In the 1980s and 1990s, the University of South Carolina continued to develop its resources to better serve the Palmetto State. A concerted drive to achieve national recognition brought Carolina into the 21st century. In 2001, the University of South Carolina celebrated a legacy of 200 years of educating leaders for the future of South Carolina, the nation, and the world.