This refuge is home to indigenous animals such as the black bear, alligator, two species of fox, bobcat, raccoon, coyote, opossum, beaver, river otter, mink, and red wolf.

The Pungo Lake unit is a notable overwintering site for Tundra swans, snow geese, and many species of ducks, with about 100,000 waterfowl in residence between November and January.

[5] On June 1, 2008, lightning struck the refuge and started a wildfire known as the Evans Road Fire that had, as of 17 September 2008[update], spread to about 40,704 acres (164.72 km2), and burned much of the same land before it was completely contained.

[9] Indigenous people likely lived nearby, and accounts from early in the refuge's documented history mention the presence of various Native American artifacts on the shores of Pungo Lake.

While tribal organization and boundaries changed rapidly during the era of colonization, as conflict and disease inflicted high mortality rates on indigenous peoples, the Secotan and Machapunga tribes are both recorded in the area.