It travels a distance of 159.8 miles (257.2 km), serving Tunica, Tate, Marshall, Benton, Tippah, Prentiss, and Tishomingo counties.

It enters some neighborhoods and turns left onto a two-lane northern bypass of the city, known as Wilson Drive.

MS 4 turns south through a mix of neighborhoods and businesses for a few blocks (along Norfleet Drive) before making a sharp left onto Main Street and immediately having an interchange with I-55 (Exit 265).

MS 4/MS 7 become S Craft Street as they widen to a four-lane for a short distance through a business district before narrowing back to two-lanes and passing through neighborhoods.

The highway now enters the outskirts of Ashland, where it immediately becomes concurrent with MS 5 and they head southward through rural areas.

The highway has an intersection with MS 371 as it passes through Hobo Station and New Site before winding its way through hilly terrain for several miles to enter Tishomingo County near its crossing of the Tennessee Tombigbee Waterway at Jamie Whitten Lock and Dam.