It runs in a north/south direction for approximately 97.6 miles (157.1 km), serving four counties: Jackson, George, Greene, and Wayne.

MS 57 begins in Jackson County on the Ocean Springs/Gautier city line in the small community of Fontainebleau at an intersection with U.S. Route 90 (US 90).

It heads north as four-lane divided highway through mostly rural woodlands, passing by some homes and businesses here and there, for a little under 3.0 miles (4.8 km) to have an interchange with Interstate 10 (I-10) at its exit 57.

The highway now narrows to two-lanes as it leaves Fontainebleau, as well as the city limits of both towns, to wind its way northward through a mix of farmland and wooded areas for several miles to pass through the community of Vancleave before paralleling the Pascagoula River along its western banks and crossing into George County.

The highway passes through the community of Leaf before crossing over a railroad track to enter the town of McLain and have an intersection with MS 198.