Cottonmouths eat both warm and cold-blooded prey, including other water snakes. Their diet includes fish, frogs, salamander, lizards, small turtles, baby alligators, birds, small mammals, and other snakes. Prey such as frogs, fish, and other snakes are held in the jaws for a few moments after capture to allow them to succumb to the venom. Mammals (which are likely to bite back) are struck and then instantly released. If the victim flees before the venom takes effect, the cottonmouth tracks it by scent. It then examines the carcass by touching it with its tongue to make sure that the prey is dead. It swallows the prey headfirst. Unlike non-venomous reptiles, the cottonmouth takes its time when feeding, perhaps because its prey is dead.
The aggressiveness of these snakes has been greatly exaggerated. In tests designed to measure the various behavioral responses by wild specimens to encounters with people, 23 of 45 (51%) tried to escape, while 28 of 36 (78%) resorted to threat displays and other defensive tactics. Only when they were picked up with a mechanical hand were they likely to bite.