In western Asheboro, NC 49 joins US 64 for a  stretch through Asheboro and the outskirts of Franklinville. In Ramseur, the two routes split; NC 49 goes north through the towns of Liberty and Alamance and into Burlington, where it meets I-40/I-85. A concurrency of NC 49 and US 70 winds through Burlington before the two routes diverge at Haw River, where NC 49 heads north.
In western Asheboro, North Carolina, U.S. Route 49 intersects with U.S. Route 64 for a stretch that passes through Asheboro and Franklinville's outskirts. In Ramseur, the two routes diverge; U.S. 49 continues north through Liberty and Alamance before reaching Burlington, where it merges with Interstate 40/Interstate 85.  U.S. Route 70 and U.S. Route 49 share a concurrency in Burlington before they separate at Haw River, with U.S. Route 49 heading north.