The refuge serves primarily as a nesting, feeding, resting and staging areas for migratory waterfowl. The varied habitats support approximately 266 species of birds, 42 species of mammals, plus reptiles, fish, amphibians and insects. Bald eagles have maintained an active nest on the refuge since 1986. Management goals also address the needs of species of special concern including black tern, black ducks, osprey, American woodcock, and peregrine falcons which use the refuge during some time of the year.

The refuge is one of over 540 National Wildlife Refuges in the United States managed by the U.S. Fish and Wildlife Service. The National Wildlife Refuge System is the only network of federal lands dedicated specifically to wildlife conservation.

Iroquois National Wildlife Refuge is a namesake of the Iroquois Indians, a Native American federation that resided in the north east. The federation was originally made up of five tribes: Cayuga, Oneida, Mohawk, Seneca and Onondaga. The Tuscarora entered the federation in the 1800's.