After the murder of his mother by the villainous robot Count Mecha, young Tetsuro has sunk into a life of street delinquency, his mind occupied solely by thoughts of vengeance. He dwells in a far-off future where humans may journey to another planet to trade their flesh for eternal mechanical bodies. His one ambition is to gather enough stolen funds to ride the Galaxy Express 999, a train that traverses space and carries passengers to the planet of robots.
One day, while fleeing from the authorities, he encounters the gorgeous Maetel, whose face bears a striking resemblance to his late mother. She proposes to take him aboard the Galaxy Express 999, granting him a robotic form and a chance to face Count Mecha. As the voyage unfolds, the pair meets an array of colorful individuals, including Captain Harlock and Queen Emeraldas, and Tetsuro gradually discovers what it really means to be human.