Interstate 20 is a major thoroughfare cutting across the state of South Carolina, linking the state with important transportation and business hubs to the north, west and south, including Atlanta, Georgia, Charlotte, North Carolina (via Interstate 77), Savannah, Georgia (via Interstate 95) and Washington, D.C. (via Interstate 95).

Interstate 20 enters the Palmetto State after crossing the Savannah River from Augusta, Georgia. Known as the J. Strom Thurmond Freeway, the highway heads northeastward, bypassing Aiken and Lexington before reaching the state capital of Columbia. It was constructed in various stages beginning in late 1963, with the final section between SC-340 and the Business Spur opening in August 1975.

At Columbia, I-20 crosses the Saluda and Broad rivers and travels through the northern part of the city and turns eastward, bypassing Fort Jackson and Camden before reaching Florence. It is at Florence where I-20 sees its eastern terminus at Interstate 95. However, for about two miles (3 km), the highway continues to downtown Florence as Business Spur 20.

In 2003, The North Carolina Department of Transportation proposed extending I-20 eastward from Florence to Wilmington at the behest of North Carolina Governor Mike Easley and his 'Strategic Transportation Plan' for the southeast portion of the state. The proposed route would follow U.S. 76 east from Florence to Whiteville, North Carolina, then parallel U.S. 74/U.S. 76 into Wilmington. Part of this route is already designated the future Interstate 74. As part of the 2005 SAFETEA-LU transportation legislation, North Carolina received $5 million for a feasibility study for this extension.

While this extension has considerable support among towns in southeastern North Carolina, the South Carolina DOT has stated that they have no interest in upgrading their portion of U.S. 76 to an interstate. This is likely due, in no small part, to encourage eastbound vacationers to travel to Myrtle Beach, South Carolina rather than Wilmington and that they are concentrating their efforts on plans to build Interstate 73 that will terminate near Myrtle Beach. Officials in Wilmington in the Fall of 2009 responded with another idea, route I-20 north along I-95 to I-74 and then be routed or co-routed with I-74/US 74 to Wilmington. State and federal officials have not officially responded to this proposal.