When Kelvin "Cornbread" Smith saves Dominic "Mo" Taylor from the jaws of a hungry alligator, the two preteen boys become fast friends. It's the summer of 1964, and they're determined to spend the sweltering days fishing for catfish and trading jokes and good-natured jabs. But this is rural Alabama, and their multiracial friendship stirs up trouble with the powers-that-be, particularly a corrupt sheriff by the name of Wayne Turner.

Cornbread's skin color makes him the target of Sheriff Turner, who orders Mr. Willie, the owner of an illegal moonshine operation, to feed Cornbread to the gator that almost got Mo. Cornbread, though, wins over Mr. Willie. And soon enough, even Mo's father, a decorated war hero who has just returned from the fighting in Vietnam, warms to his charms.

As Mo's friendship with Cornbread continues to provoke the predominantly white community, the adults in their lives are forced to come to grips with their own prejudices. Mr. Willie's heart softens, and Mo's father endeavors to make up for his racist past. The clash of values threatens to become deadly when the sheriff and a ruthless outsider try to force Mr. Willie to expand his moonshine operation. Only Mo and Cornbread can save Mr. Willie-and stop the sheriff.