The highway now passes through more neighborhoods before leaving West Point and traveling east-southeast through farmland for several miles to the community of Waverly, where it crosses a bridge over the Tombigbee River (Tennessee Tombigbee Waterway) into Lowndes County.

The highway enters the Columbus city limits as an undivided four-lane and soon passes through a long major business district for a few miles to come to an interchange with US 82 (unsigned MS 12) just north of downtown, with US 45 heading west along US 82, MS 50 heading east along US 82, and the road continuing into downtown as MS 69 (N 5th Street).

US 82/MS 12/MS 50 head east along a four-lane freeway that bypasses the entire downtown area on its north side, having interchanges with 18th Avenue N and Military Road (as well as crossing Luxapallila Creek).

MS 12/MS 50 split off from US 82 at an interchange with Tuscaloosa Road, heading east as a four-lane boulevard through a business district for not even a mile to an intersection where MS 12 splits off and heads north.

MS 50 now narrows to two-lanes and leaves Columbus, traveling through farmland for several miles to come to the Alabama state line southeast of Steens, with the road continuing into Alabama as State Route 96 (SR 96).