U.S. Federal Route 278 runs north-south from the Coahoma/Bolivar County Line to near Lyon. At Lyon is runs east-west to the Coahoma/Quitman County Line. U.S. Rt. 278 passes through the following town in Coahoma County. Clarksdale
U.S. Rt. 278 is multi-plexed in Coahoma County. U.S. Rt. 61, from the Coahoma/Bolivar County Line to near Lyon.