It connects the communities of Hinkle, Pisgah, and Jacinto with the town of Rienzi.

It heads east through a mix of farmland and woodlands, traveling over gently rolling hills for a few miles to have an intersection with US 45 and enter the town of Rienzi.

The highway makes a sharp left onto Main Street, at an intersection with County Roads 443 (Robbins Street) and 442, before passing through a neighborhood.

Leaving Rienzi, the highway crosses the Tuscumbia River and winds its way through hilly wooded terrain for the next several miles to pass through the community of Jacinto and have an intersection with MS 367.

MS 356 enters Prentiss County and comes to an end a few miles later at an intersection, just two miles west of the "Divide Cut" of the Tennessee Tombigbee Waterway.