After being imprisoned for 10 years, the "Devil's Rejects" are back at it again. Otis (Bill Moseley) escapes prison, meets Winslow (Richard Brake), and devises a plan to get his sister Baby (Sheri Moon Zombie) out too. The Rejects make their way down the road and into Mexico, killing countless people on their way. They find a place to stay, but are soon bombarded with a large group of killers- killers who are after these Three From Hell. Only one group can come out alive, and with the experience these three have, it'll just have to be one great killing joyride.