U.S. Federal Route 64 runs east-west across the southern portion of Cherokee County. The majority of this route throughout the conty is a multi-lane divided highway. U.S. Rt 64 passes through the following town in Cherokee County. Ranger U.S. Rt. 64 is multi-plexed in Cherokee County. U.S. Rt. 74, from the Tennessee/North Carolina State Line to near Murphy.
U.S. Rt. 19, from near Ranger to near Murphy. U.S. Rt. 129, from near Ranger to near Murphy.