Established in late 1934 as a renumbering of NC 15, it traversed from Lake Wylie to Morehead and Tryon Street, in Charlotte, where it connected with US 21/US 29/US 74/NC 27. In 1940, NC 49 was extended northeast from Charlotte to the Virginia state line, near Virgilina, Virginia; its routing went as followed: In Charlotte, it was overlapped with US 29 along Tryon Street and Old Concord Road. Traveling through Concord, via Old Charlotte Road, it then overlaps with NC 73 to Mount Pleasant. Replacing NC 62, it travels northeast, through Richfield and Farmer, to Asheboro. With a brief overlap with US 220 (Fayetteville Street), it continues its northeasterly along Old Liberty road, replacing NC 62, through Liberty, Graham, Haw River, to Pleasant Grove. Going east from Pleasant Grove, NC 49 replaced NC 144, through Roxboro, to the Virginia state line, near Virgilina.