Tetsuro Hoshino, orphaned by the Cyborgs, lives in a slum in the shadow of their megapolis. He steals a pass for Galaxy Express 999, and is saved by a mysterious woman called Maitre, a living image of his mother who had been killed by the Cyborgs. Wearing a special pendant, he sets out for Andromeda where he can obtain eternal life and avenge his parents' death. On his odyssey, he meets a gallery of fantastic characters that help him exterminate the evil Star of Andromeda which had been giving mechanical bodies to rich human beings.