Set in the second half of the 22nd century, in the year 2176, the film depicts Mars as a planet that has been 84% terraformed, allowing humans to walk on the surface without wearing pressure suits. The story concerns a police officer, Melanie Ballard (Natasha Henstridge), second in command of a small team sent to pick up and transport a prisoner named Desolation Williams (Ice Cube). Arriving at the remote mining town where Williams is being held, Ballard finds virtually all of the people missing. She learns that the miners had discovered an underground doorway created by an ancient Martian civilization. When the door was opened it released "ghosts", disembodied spirits who possessed the miners.
Violence ensues, as the possessed miners commit acts of death and destruction, as well as self-mutilation. Ballard must fight off the attacking miners, escape the town, and destroy the ghosts, if possible. Unfortunately, her intentions are complicated by the fact that killing a possessed human merely releases the Martian spirit to possess another human. The team eventually decides to blow up a nuclear reactor to kill the human hosts. Ballard's crew is eventually wiped out by the miners, leaving only her and Williams. Not wanting the authorities to blame the massacre on him, he handcuffs Ballard to her bed and escapes the train, leaving her to return home. While she recuperates at a hospital, the released spirits attack the city. Williams returns and teams up with Ballard to fight the possessed.