Thirty-six species of mammals are known to occur on the refuge. Beaver are common, moose occur in relatively low numbers, and black and grizzly bears can be found anywhere. Tracks of wolves and other furbearers, such as American marten, fox, and river otter are commonly seen in winter, but these species are difficult to observe during the summer months. Caribou often winter on the Refuge, although usually in low numbers.
At least 150 species of birds have been recorded on the refuge or nearby in Bettles, of which fewer than 20 are likely year round residents. The Koyukuk and Kanuti Rivers and their associated wetlands provide productive breeding habitat for many species of waterfowl and waterbirds.
Seventeen species of fish, some of which are extremely important subsistence resources, are known to occur in waters within the refuge.
With 26 species documented to date, one of the top areas for dragonfly diversity in Alaska is Kanuti National Wildlife Refuge.