Corn snakes' preferred diet consists primarily of small mammals, particularly rodents. In the wild, they commonly feed on mice, rats, and other small rodents suitable for their size. Studies on the feeding habits of corn snakes suggest that they play a crucial role in controlling rodent populations.

Corn snakes are opportunistic feeders, meaning they will eat a variety of prey when available. Apart from rodents, they may consume unguarded bird eggs, birds, reptiles, amphibians, and invertebrates.

Corn snakes, like many colubrid snakes, are not venomous because they lack the specialized glands and fangs required for venom production and delivery. Instead, they are constrictors, which means they subdue their prey through constriction rather than venom injection. Corn snakes have powerful muscles and flexible bodies that can overpower their game.

A corn snake detects potential prey by using its keen sense of smell and flicking its tongue to pick up scent particles in the air. When the time is right, the corn snake strikes, seizing the prey with its sharp teeth and coiling its body around it. They then swallow their prey whole, usually head first.

The illegal pet trade has a devastating impact on the ecosystem. One of its consequences has been the unregulated spread of the red rat snake beyond its native habitats in North America, enabling it to establish new colonies in different regions. 

In Australia, the corn snake is listed as an invasive species. The species appears to thrive despite capturing 79 of them between 2002 and 20141.