Mississippi Highway 321 (MS 321) is a state highway consisting of two segments, one connecting Webb to Brazil in Tallahatchie County, the other in Quitman County in and around Lambert.

The two-lane state maintained highway[2] heads north eventually paralleling the Tallahatchie River.

In the unincorporated community of Brazil, state maintenance ends before the road, continuing north as Brazil Quitman County Road, crosses Buzzard Bayou.

The intersection is located near the former Camp B of the Mississippi State Penitentiary, now mostly the O'Keefe Wildlife Management Area.

In the town, MS 321 carries the name 6th Street and passes by houses and churches.