Loosely based on Homer's "Odyssey," the film follows the picaresque adventures of Ulysses Everett McGill and his companions Delmar and Pete in Mississippi in the 1930s. Emerging from a chain of gangs and trying to get to Everett's house to recover buried loot from a bank robbery, they will face a series of strange characters, including mermaids, a cyclops, the bank robber George "Baby Face" Nelson (much annoyed by that nickname), a campaigning governor and his opponent, a KKK lynch mob, and a blind prophet who warns the trio that "the treasure you seek is not the treasure you find."