The highway connects Cottageville with rural areas of Colleton County.

SC 651 begins at an intersection with U.S. Route 17 Alternate (US 17 Alt.

It travels to the north-northeast and almost immediately leaves the city limits.

The highway curves to the north-northwest and then heads on a fairly northerly direction before crossing over Horse Pen Branch.

It curves again to the north-northwest and meets its northern terminus, an intersection with SC 61 (Augusta Highway).