Panther Swamp NWR, established in 1978, with over 38,500 acres, contains one of the few remaining large tracts of mature bottomland hardwoods in the delta of Mississippi. Much of the habitat is subject to flooding on an annual basis. The refuge has a number of bayous that slowly drain flood waters, leaving shallow swamps and oxbow lakes which support stands of tupelo gum, cypress, buttonbush, and other species tolerant to extremely wet habitats.

The upland areas or ridges often crest at no more than one foot above swamp areas, and contain nuttall, willow and water oaks and other species while overcup oak, bitter pecan and ash dominate the transition zone from swamp to upland. Additional habitat types consist of reforested and agricultural areas. Crops left in the field are used to support large concentrations of wintering waterfowl.

The refuge supports healthy populations of resident wildlife and neotropical migrants. Hunting seasons are established for waterfowl and all native game species, which includes white-tail deer, fox and grey squirrels, swamp and cottontail rabbits, raccoon, opossum, and the wild turkey. The endangered Louisiana Black Bear is occasionally observed on the refuge.