SC 53 begins at an intersection with US 378 (Myrtle Beach Highway) southwest of Shiloh, within Sumter County.

It travels to the northeast, through rural areas of the county, and curves to a nearly due east direction.

It intersects SC 58 (Pleasant Grove Road), and the two highways begin a concurrency.

Approximately 500 feet (150 m) later, SC 53 splits off to the south, onto Pudding Swamp Road.

About 2,000 feet (610 m) later is the highway's northern terminus, an intersection with SC 403 (Lynches River Road/Amwell Church Road).