The Interstate Highway is the primary connection between the Greater Richmond Region and Research Triangle and other major metropolitan areas of North Carolina.

Northbound I-85 has a welcome center before the highway crosses Lake Gaston, an impoundment of the Roanoke River, on a causeway and bridge before reaching an interchange with State Route 903 (SR 903) at Bracey.

US 58 serves as the major east–west highway of Southside; the US Route provides access to La Crosse, Brodnax, Lawrenceville, and Emporia to the east and Boydton and Clarksville to the west.

North of the town of South Hill, I-85 has a junction with US 1 (Mecklenburg Avenue), which parallels the Interstate Highway from Henderson to Petersburg.

At the partial cloverleaf interchange with US 460, which also leads to Dinwiddie County Airport, the Interstate Highway and US Route start to run concurrently toward Petersburg.

Both the US 460 interchange and the following partial cloverleaf junction with US 1 (Boydton Plank Road) provide access to the National Museum of the Civil War Soldier at Pamplin Historical Park.