دوره تایشو در ژاپن است. تانجیرو، پسر مهربانی که برای امرار معاش زغال می‌فروشد، خانواده‌اش را می‌بیند که توسط یک شیطان سلاخی شده‌اند. بدتر از همه، خواهر کوچکترش نزوکو، تنها بازمانده، خود به یک شیطان تبدیل شده است. اگرچه تانجیرو از این واقعیت تلخ شوکه شده است، اما تصمیم می‌گیرد که تبدیل به یک «شیطان‌کش» شود تا بتواند خواهرش را دوباره به یک انسان تبدیل کند و شیطانی که خانواده او را قتل عام کرد، بکشد.

In a distant future, Tetsuro is a human boy who wants his body replaced with a robotic one. This is possible, but to do so he has to reach the Immortal Planet onboard the space train Galaxy Express 999. Maetel, a beautiful and mysterious blonde woman dressed in Russian style, joins him in the long journey through space. Every episode sees our heroes arriving in a new planet's space train station.

Twins Kazuya and Tatsuya, and their neighbor Minami have played together since they were children and built an unbreakable bond. But with puberty, the twins realized something: Minami is a girl, and three is a crowd.

As the trio tries to preserve their relationship, Kazuya's pledge to make Minami's dream come true by taking her to Koshien with his baseball pitching skills makes the slackerish Tatsuya wonder about himself, and his own goals. But Minami has another dream she wants fulfilled, and as the twins continue to push themselves, with Minami in the middle, a life-changing tragedy leads one twin down a path he once never would've considered...