U.S. Route 52 is a North–South U.S. Highway that runs 161 miles (259 km) from Charleston to the North Carolina state line near Cheraw. It serves as a strategic highway through the central South Carolina.

U.S. 52 enters South Carolina northeast of Cheraw. From Darlington southward it is a multilane highway and Freeway, passing through Florence, Lake City, Kingstree, Moncks Corner and North Charleston before U.S. 52's terminus at number 2 Meeting Street and White Point Gardens in Charleston.