Even after the destruction of Andromeda, their mechanized homeworld, the machine empire continues expanding its influence, turning Earth into a war zone. Tetsurou Hoshino, who once journeyed on the Galaxy Express 999, now joins other humans resisting the mechanical takeover.
When the 999 returns to Earth, Tetsurou gets a mysterious message from Maetel, his former travel companion, telling him to get back on the train. Fighting through enemy forces to reach Megalopolis station, he barely boards the departing train. But this trip brings fresh obstacles: Maetel is missing, a threatening "Ghost Train" appears, and the 999's final stop remains unknown. Along the way, Tetsurou confronts the enigmatic black knight Faust and learns the machine empire's most hidden truths.