is a 3.420 miles (5.504 km) business route of US 521 that travels through downtown Andrews, via Main Street.

[citation needed] The entire route is in Georgetown County.

The highway takes various roads including: Ehrenclou Drive, Chestnut Ferry Road, Jefferson Davis Highway (in concurrency with US 1/US 601/SC 34), Springdale Drive, and Boykin Road (in concurrency with US 601 Truck).

Nearly the entire length of the truck route is within the city limits of Camden.

[citation needed] The entire route is in Lancaster County.

It connects US 521 (North Matson Street) with US 521 Business (US 521 Bus.)

U.S. Route 521 Connector (US 521) was a 4.7 miles (7.6 km) connector route that went east around Sumter along Guignard Drive, connecting to US 15, in the southern end of Sumter.

was the bypass around downtown Lancaster, until the mainline was realigned in 1965, and the former route was converted into US 521 Business (US 521 Bus.