NC 49 is a state highway in the North Carolina Highway System that traverses much of the Piedmont region of North Carolina.

The highway runs from near Lake Wylie, south of Charlotte, to Virgilina on the Virginia state line.

The route is an important corridor for traffic as it forms a part of the shortest route between Charlotte, the largest city in the Carolinas, and the North Carolina state capital of Raleigh. NC 49 meets US 64 in Asheboro, which forms the majority of the Charlotte-Raleigh link.

From its southern terminus, the highway passes through Charlotte and after crossing the more suburban portions of western Cabarrus County, heads north east into Stanly County. From uptown Charlotte to University City NC 49 is concurrent with US 29. After passing Mount Pleasant in eastern Cabarrus County, the road becomes a designated North Carolina Scenic Byway. The road passes close to Pfeiffer University in Stanly County before crossing the Yadkin River near the Tuckertown Reservoir. After crossing the river, the road skirts the northern foothills of the ancient Uwharrie Mountains and then drops down into the Asheboro area.

In western Asheboro, NC 49 joins US 64 for a 12-mile (19 km) stretch through Asheboro and the outskirts of Franklinville. In Ramseur, the two routes split; NC 49 voyages north through the towns of Liberty and Alamance and into Burlington, where it meets I-40/85. A concurrency of NC 49 and US 70 winds through Burlington and Haw River, where NC 49 splits to the north. In northern Alamance County, NC 49 meets a 4-way at-grade junction with NC 62. The two routes switch directions at this point; NC 49 darts east toward Roxboro. After passing through Roxboro and a short concurrency with US 158 and US 501, NC 49 continues on its final leg to the Virginia state line.

One unique fact about the route is that NC 49 is one of limited number of state highways that maintain their numbers in more than two consecutive states, which in this case is Virginia (VA 49) and South Carolina (SC 49).