U.S. Federal Route 61 runs north-south in Coahoma County. This is a four-lane divided highway through out Coahoma County. The Clarksdale by-pass is a limted access highway. U.S. Rt. 61 passes through the following town in Coahoma County. Clarksdale U.S. Rt. 61 is multi-plexed in Coahoma County. U.S. Rt. 49, from near Rich to Clarksdale.
U.S. Rt. 278, from near Lyon to the Coahmoa/Bolivar County Line.
Branches of U.S. Rt. 61 in Coahoma County. A junction marker on SB U.S. Rt. 49. SB U.S. Rt. 49/61 near Coahoma. NB U.S. Rt. 49/61; EB U.S. Rt. 278 near Clarksdale.