Monomoy supports and array of mammals, birds, reptiles and sea life. Coyotes, deer, muskrats and voles are among the mammals who occupy the refuge lands. Monomy provides a particularly desirable habitat for seals. Harbor seals may be spotted of the coast of Monomy from August until May, while nearly 5,000 gray seals call Monomy home all year-long. As a Western Hemisphere Shorebird Reserve Network Regional site, Monomy has worked to provide a safe gull free zone for shore and seabirds.

Monomoy is one of the most diverse waterfowl areas in Massachusetts. Throughout late August and into early September, visitors to refuge may find adult and juvenile black ducks, blue- and green-winged teal, mallards, gadwall and northern shovelers. Throughout mid September teal, northern pintail and American widgeon appear more regularly. Finally, through October and November eider, oldsquaw and scoter may be found. During these prime months more than 1,000 waterfowl may be spotted at the refuge.