I-40 - This interstate runs east to west through southern Forsyth County. As it enters Forsyth County from the east near Piedmont Triad International Airport, I-40 splits into Business I-40 and I-40 Bypass. Business I-40 travels near Kernersville and Walkertown before heading into the heart of downtown Winston-Salem, intersecting with U.S. 52 and then heading on to the retail center of Stratford Road and Hanes Mall Blvd.  I-40 bypass travels to the south near High Point, intersecting with U.S. 311 and then rejoining with Business I-40 at its intersection with U.S. Highway 421.

U.S. 52 - Traveling along a north to south route, this highway intersects with  I- 77 as it enters North Carolina from Virginia. U.S. 52 travels south, passing through Mt. Airy, King, Tobaccoville, and Rural Hall, before running through downtown Winston-Salem, then intersecting with both Business I-40 and I-40 Bypass. U.S. 52 travels just a few miles on farther to Lexington, where it joins with I- 85 heading toward Charlotte. Sections of the highway are the future corridor of I- 74 that will connect Winston-Salem to the Midwest and Canada and to Charleston, South Carolina to the south.