Holly Springs was founded in 1835 by William Randolph of Virginia at the site of several springs encircled by holly trees. Its fine antebellum homes can be viewed during the annual pilgrimage in April. During the American Civil War more than 60 skirmishes were fought there, including a raid by Confederate General Earl Van Dorn (December 1862) that destroyed a Union supply depot and delayed the Union drive to Vicksburg. A yellow-fever epidemic in 1878 killed hundreds of residents.

Cotton remains important in Holly Springs. Manufactures include plastics, filtration equipment, and windows, and electrical equipment is made in nearby Byhalia. Holly Springs is the seat of Rust College (1866). Its Kate Freeman Clark Art Gallery houses more than a thousand paintings by that artist, who was a native of the city. Holly Springs National Forest and Wall Doxey State Park are nearby. The Kudzu Festival is held in July. Inc. 1837. Pop. (1990) 7,261; (2000) 7,957.