The story is set within the Zone of the Enders universe. It is 2173 and humankind, in the search for a valuable resource called Metatron, has expanded its reaches to Mars and the moons of Jupiter, and full colonies have been established. However, Earth keeps a tight rein over the colonials, known by the derogatory term "Enders", and discrimination is commonplace. Food supplies are short, movement of citizens is controlled, and many Mars inhabitants have tried to rise up against Earth, but to little avail. The game follows the story of a 17-year-old boy named Cage Midwell, a worker upon the interplanetary express ship "Bonaparte III" with his close friend (and idol) Ares Enduwa. However, on a routine journey, Cage spots a woman creeping into the cargo holds, and follows her. As he does this, the ship is attacked by a powerful black Orbital Frame. Cage and the girl, who introduces herself as Myona Alderan, climb into a mysterious LEV held within the ship and escape, eventually crash-landing on Mars. They are quickly caught and are accused of being the ones responsible for the crash. On top of this, Myona has completely lost her memory. However, shortly after their imprisonment, they are freed by an "Anti-Terrestrial League" leader called Deckson Geyse. His faction, BIS (Born In Space), quickly come and rescue them, and Cage finds himself caught up in the escalating conflict between Earth and Mars.