Two doctors find their graveyard shift inundated with townspeople ravaged by sores. Among the wounded is Cherry Darling, a dancer whose leg was ripped from her body. As the invalids quickly become enraged aggressors, Cherry and her ex-boyfriend El Wray lead a team of accidental warriors into the night.

Grindhouse combines Robert Rodriguez's Planet Terror, a horror comedy about a group of survivors who battle zombie-like creatures, and Quentin Tarantino's Death Proof, an action thriller about a murderous stuntman who kills young women with modified vehicles. It is presented as a double feature with fictitious exploitation trailers before each segment.