The highway heads east as a two-lane highway, known as Main Street, through a neighborhood before making a sharp left turn at an intersection with MS 782 in downtown.

It passes north through downtown before curving back eastward to have an intersection with MS 15.

The highway now leaves Mantee and heads east through farmland to cross into Clay County, just prior to its interchange with the Natchez Trace Parkway.

It makes a sharp right in the center of the community before leaving Montpelier and winding its way southeast through farmland for several miles to pass through Beasley, where the former central section of MS 389 (Pheba-Beasley Road) departs southward toward Pheba.

The highway travels southeast through a mix of rural farmland and woodlands for several miles before MS 46 comes to an end at an intersection with MS 50 just five miles west of West Point.