At the end of the Ice Age, The Machine came from outer space with the purpose to change men into mutants. However, a hero defeated the device and a great seal was laid over The Machine. In 2707, the depleted world is ruled by four Corporations: Mishima, Bauhaus, Capitol and Imperial that are in a constant state of war. During a battle between Capitol and Bauhaus, the great seal is broken and The Machine works again transforming soldiers and civilians into hordes of mutants. A small part of the population escapes to Mars, leaving millions of people behind. The man of faith and leader of an ancient brotherhood, Brother Samuel, is a believer in God and the Chronicles, a bible about the mutants from ancient times. With the city besieged by the mutants, he visits the Corporations' leader Constantine, asking for an aircraft and twenty men for a suicide mission to destroy The Machine, planting a bomb and a detonator following the knowledge of the Chronicles...

A number of fighters are invited to DOA, an invitational martial arts contest. They travel to the tournament island by plane, until they have to jump out mid-flight with parachutes, and then have until sundown to reach the main island to be entered into the tournament. Fighters are then pooled against one another in a knock-out style tournament, with the loser of a battle sent home, and the winner progressing to the subsequent round. The plot revolves around four female fighters who begin as rivals, but subsequently find themselves teaming up against another force.