The basin's dense bottomland hardwoods, Bald Cypress-Tupelo swamps, overflow lakes, and meandering bayous provide a tremendous diversity of habitat for more than 200 species of resident and migratory birds and numerous other wildlife and the area has been recognized as an Internationally Important Bird Area.

Wild turkeys, white-tailed deer, eastern gray and fox squirrels, eastern cottontail, swamp rabbit, gray and red fox, coyote, striped skunk, and Virginia opossum inhabit the refuge, as do a small remnant population of Louisiana black bears.

The combined area of the refuge, totaling 44,000 acres (180 km2), classified as bottomland hardwoods, contains four dominant tree species associations: (1) cottonwood and sycamore, (2) oak, gum (American sweetgum or redgum), hackberry (sugarberry or sugar hackberry), ash (swamp or water ash), (3) willow (black willow), bald cypress, pumpkin ash, (4) overcup oak, and bitter pecan or water hickory.

Due to the flooding of the Mississippi River and the opening of the Morganza Floodway the refuge was closed to the public May 14, 2011.

Although most of the refuge remains closed the South Farm (Iberville Parish) portion of the Sherburne WMA was open July 1, 2011, to walk-in and ATV traffic.