Fort Hill was the home of John C. Calhoun, South Carolina's pre-eminent 19th century statesman, from 1825 until his death in 1850. The antebellum plantation home, office and kitchen are furnished mostly with family artifacts.

John Caldwell Calhoun's national political career spanned 40 years from 1810 to 1850. His service in the national government included: United States representative (1811-1817); secretary of war to President James Monroe (1817-1825); vice president to President John Quincy Adams (1825-1829); vice president to President Andrew Jackson (1829-1832); United States senator (1832-1843); secretary of state to President John Tyler (1844-1845) and United States senator (1845-1850).

Thomas Green Clemson, Calhoun's son-in-law and founder of the University, envisioned "the preservation of the home of the illustrious man who spent his life in the public service of his country." In his 1888 will, Clemson bequeathed more than 814 acres of the Fort Hill estate to the State of South Carolina for an agricultural college with a stipulation that the dwelling house "shall never be torn down or altered; but shall be kept in repair with all articles of furniture and vesture... and shall always be open for inspection of visitors." Clemson University has operated Fort Hill as a house museum as stipulated in the will. Fort Hill, designated a National Historic Landmark in 1960, was named a national treasure by the Save America's Treasures program in 2003.