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 northern Alamance County, NC 49 meets NC 62 at a 4-way at-grade junction. The two routes switch directions at this point; NC 49 turns east toward Roxboro. After passing through Roxboro and a short interval of concurrency with US 158 and US 501, NC 49 continues on toward the Virginia state line.