U.S. Federal Route 74 runs east-west across the western portion of this county. Near the center, it turns and heads in a northern direction toward Macon and Swain Counties. U.S. Rt. 74 passes through the following towns in Cherokee County. Ranger Murphy
U.S. Rt. 74 is multi-plexed in Cherokee County. U.S. Rt. 64, from the Tennessee/North Carolina State Line to near Murphy.
U.S. Rt. 19, from near Ranger to the Macon/Cherokee County Line.
U.S. Rt. 129, from near Ranger to the Macon/Cherokee County Line.