It runs from east to west for 177.654 miles (285.906 km), serving 7 counties: Claiborne, Copiah, Hinds, Rankin, Smith, Jasper, and Clarke.

US 80/MS 18 pass through a mix business districts and neighborhoods for a few miles as they travel just to the south of Jackson State University, while paralleling I-20/I-55 just to the north.

The highway passes through some neighborhoods before entering a business district, where MS 18 splits off and heads south to have another interchange with I-20 (Exit 54) before narrowing to two-lanes.

The highway has an intersection with Louis Wilson Drive (Old MS 18) before leaving Brandon and traveling southeast through a mix of rural farmland and woodlands for the next several miles.

The highway now leaves Raleigh and travels through more woodlands to cross the Leaf River and have an intersection with MS 501 before passing through the village of Sylvarena.

The highway leaves Pachuta and travels east through a mix of farmland and woodlands for several miles to become concurrent with MS 145 and they head north to cross the Chickasawhay River into Quitman.