Completed in 1859, the observatory is named after prominent University of Mississippi professor and former university president Fredrick A. Barnard, who commissioned the building. Barnard Observatory serves as a testament to the university's original architecture and has been used for various facets throughout its history including serving as a hospital for both Confederate and Union soldiers during the Civil War, a classroom, a sorority house, the physics department, a theatre stage, and presently the Center for the Study of Southern Culture. In 1979, Barnard Observatory was listed on the National Register of Historic Places, and in 1986, it became a Mississippi Landmark. A $3 million renovation began in 1989 and was completed in 1992.

Built in 1889, Ventress Hall is a testament to the University of Mississippi's original Victorian architecture and has served as the home of many departments over the centuries. It was first the university library. It then served as the home of the School of Law from 1911 until 1929, when it was utilized by the State Geological Survey. Starting in 1963, it became the Department of Geology, and in the 1970s, the Department of Art. The College of Liberal Arts has been housed in the historic building since 1998.

During the Civil War, the University of Mississippi closed its doors as many of its students enlisted in the Confederate army, most notably as members of the University Greys and Lamar Rifles companies. In 1906, the United Daughters of the Confederacy dedicated a 29-foot Confederate monument at the entrance to the university. Ostensibly dedicated to local veterans, both the monument itself and the dedication ceremony were imbued with support for the "Lost Cause" interpretation of history which sought to vindicate the antebellum South and the Confederacy. In 1962, white student rioters protesting against racial integration at the university chose to gather around this monument. In recent years, as more students and alumni have learned about the connection between Confederate Monuments and support for the Lost Cause, there have been increasing calls for the monument's reinterpretation and/or relocation. On July 14, 2020, the University of Mississippi relocated the monument to the on-campus Confederate cemetery, which is located off the Coliseum Loop. Debates over the best way to interpret this and other Confederate symbols continue as members of the university community discuss topics such as the history of the University during the Civil Rights Movement and the connection between the University and slavery.

Located in a historic church, the Burns-Belfry Museum and Multicultural Center aims to preserve the cultural history of Oxford, particularly the town's African American history. It serves as a museum and meeting place for non-profit organizations. The Center is operated by the Oxford-Lafayette County Heritage Foundation, which was established in 1996. The church building itself was constructed in 1910 by an African American Episcopal congregation, replacing an earlier wooden structure that had become too small. The museum currently features an exhibit about the area's African American history, but plans are in place to create other exhibits that explore other cultures such as the Chicksaw Indians and settlers.

Constructed in 1844, Rowan Oak was the home of William Faulkner from 1930-1962. Faulkner was one of the 20th century's greatest writers, best known for his novels As I Lay Dying and The Sound and the Fury. He earned the Nobel Prize in literature in 1950 and the Pullitzer Prize in 1955 and 1963 (posthumously). The estate became a National Historic Landmark in 1968. The University of Mississippi acquired the property in 1972 and operates the home as a museum dedicated to preserving and interpreting the life of one of America's most-influential novelists.