The highway runs generally southeast from the central part of South Carolina to near the Atlantic Ocean and is listed as a hurricane evacuation route.

[1] Beginning at a junction with U.S. Highway 52 in Moncks Corner, the route runs northwest along the shoreline of Lake Moultrie as West Main Street.

It turns left onto "Old Number Six Highway" where is later starts a concurrency with SC 45 as Eutaw Road.

It turns right on St. Matthews Road in a northwesterly direction, passing through Swansea as 2nd Street intersecting U.S. Route 321 in town and joining a concurrency with SC 302 as Edmund Hwy.

The concurrency ends when SC 6 turns to the left onto S. Lake Drive where it heads northwest to Red Bank.

The route then passes through Lexington where it briefly separates into a one-way street pair.

SC 6 passes just east of Lake Murray (over the Saluda Dam as a divided highway).

In Irmo, SC 6 changes from N. Lake Drive to Dreher Shoals Road before ending at a junction with U.S. Highway 76 in Ballentine.

The last section of the route runs south and west of Columbia, the state capital.

Counties traversed by the route include Berkeley, Orangeburg, Calhoun, Lexington, and Richland.

They travel on a bridge over some railroad tracks of CSX and then pass Berkeley Middle School.