Located in the upper end of the lower Mississippi River valley, Mingo National Wildlife Refuge, at 21,592 acres, is the largest remnant of bottomland hardwoods remaining out of an original 2 1/2 million acres in the Missouri bootheel. A major migration and wintering area for migratory waterfowl, populations of 125,000 mallards and 75,000 Canada geese have been recorded. Bald eagles have been successively nesting on the refuge since 1985.

The refuge contains approximately 15,000 acres of bottomland hardwoods, 1,000 acres of upland hardwoods, 1,275 acres of cropland and moist soil units (see Management Activities), 700 acres of grasslands, and 5,000 acres of marsh and water. There are seven natural areas on the refuge and over 140 identified archaeological sites. In 1976, 7,730 acres were designated as a wilderness area.

An additional 1,200 acres are maintained as cropland or moist soil units which can be seasonally flooded for migrating waterfowl. About 700 acres of grassland are maintained as warm and cool season grasses to provide browse for geese and deer. The 7,730-acre Wilderness Area within the refuge is managed to maintain its integrity by regulating public use and protect in air and water resources.

The University of Missouri-Gaylord Lab, located adjacent to the refuge, directs or assists with numerous wildlife studies and surveys, including banding and disease monitoring work. The 7,000-acre Duck Creek Wildlife Management Conservation Area, managed by the Missouri Department of Conservation, has a common boundary with the refuge and provides many hunting and fishing opportunities.