[4] The vast majority of the landscape along the route is farmland, with the exception in and around Timmonsville.

[5][6][7] SC 403 was established in 1933 as a renumbering of US 301 from US 76 in Timmonsville to US 15 at Lees Crossroads.

In 1948, SC 403 was retracted back to its original routing, leaving behind Hill Road (S-21-38).

Between 2005 and 2012, US 15 was realigned its Lees Crossroads intersection, removing an intersection corner bypass, giving an odd overlap with SC 403 for 0.2 miles (0.32 km) to where the corner bypass originally reconnected.

South Carolina Highway 309 (SC 309) was an 11.9-mile (19.2 km) state highway that was established in 1940 as a new primary routing, from SC 341 in Hobbs Crossroads, southeast to U.S. Route 301 (US 301).