Morgan Brake NWR, established in 1977, encompasses 7,381 acres in west central Mississippi. It is situated on the extreme eastern edge of the Mississippi/Yazoo River Alluvial Plain between U.S. Highway 49 and the adjacent loess hills in Holmes County.

The refuge was originally established to protect hardwood bottoms for use as an inviolate sanctuary, and other management purposes for migratory birds. Habitat types include 3,134 acres of bottomland hardwoods interspersed with cypress/tupelo brakes, 1,621 acres of early succession reforested areas, 813 acres of former commercial catfish ponds, 536 acres of croplands, 677 acres of shrub swamp and marsh, 570 acres of forested uplands, and 30 acres of administrative lands. The majority of the former catfish ponds are managed in moist soil, mudflat, and agriculture habitats for migratory birds, except for approximately 67 acres that have been modified and stocked with game fish for public fishing.

The refuge is noted for large numbers of wintering waterfowl, which have exceeded 100,000 ducks in recent years and as a stop-over for neotropical migrants. Resident wildlife, which includes white-tailed deer, turkey, quail, raccoons, bobcats, coyotes, otters, minks, cottontail rabbits, etc are also found throughout the refuge. Hunting seasons are established for waterfowl and native game species on certain areas of the refuge.