It is a north–south highway that travels from Walterboro to the North Carolina state line, north-northeast of McColl.

It runs parallel to Interstate 95 (I-95) intersecting with US 78 in St. George and later one of its auxiliary routes US 178 before it crosses I-26 at a cloverleaf interchange (exit 172) in Harleyville.

Then it turns northwest, passing through Wells where it not only intersects US 176, but the western terminus of South Carolina Highway 45.

As the routes turn east, the roadway continues north as US 15 Connector to service Santee.

[10] For a brief period from 1950 to 1951, US 15 was extended south from Walterboro through Yemassee and into Pocotaligo along what is today part of US 17 Alt.