From Camden to the North Carolina border, US 1 is the highest capacity route through much of the Sandhills region.

After several at-grade intersections, there is an interchange with I-520, and the route bypasses the Aiken County communities of Clearwater (where US 278 leaves the concurrency), Burnettown, and Gloverville.

This area is heavily developed, with shopping centers and subdivision entrances along both sides of the road.

York Street is a four-lane boulevard until it meets Hampton Avenue, where it leaves the main grid of central Aiken and becomes a five-lane boulevard with a center turn lane through a light industrial area leading north out of the city.

It passes into Saluda County in Moneta, and then on through the town of Batesburg-Leesville as Columbia Avenue, where it gains a center turn lane.

Passing through a large rural area, the road once again widens to a five-lane boulevard with a center turning lane as it approaches Lexington.

US 1 passes east–west through the communities of Oak Grove and West Columbia before crossing the Congaree River along the Gervais Street Bridge.

After the river, US 1 goes through downtown Columbia along Gervais Street, passing directly in front of the South Carolina State House.

[8] The entire route is part of the Jefferson Davis Highway, named after Civil War Confederate leader Jefferson Davis; with exception between North Augusta and Aiken, where US 1 was realigned, leaving SC 421 its section of the highway name.