It is situated 2 miles (3.2 km) east of Manila, Arkansas, and consists mostly of a shallow lake, swamp, and bottomland hardwood forests.
The region was known to the first White settlers as the "Great Swamp" and consisted of hardwood forests, especially bald cypress, wooded swampland, and open water.
The large network of man-made ditches in the Missouri bootheel region drains 2,500 square miles (6,500 km2) of former swamp land.
Silt from agricultural lands was impacting Big Lake, but in the 1990s the U.S. Army Corps of Engineers undertook to divert silt-laden water around the refuge.
The drier parts of the refuge are also forested in hardwoods, including several species of oak, green ash, cottonwood, river birch and red maple.
Other animals found include the river otter, beaver, raccoon, wild turkey, white-tailed deer, bobcat and occasionally armadillo.
The Arkansas record largemouth bass, weighing 16 pounds 8 ounces (7.5 kg), was caught in the refuge in 1976.
Contiguous with the refuge on the east is the Big Lake Wildlife Management Area, owned by the state of Arkansas.