Japan has become a wasteland devastated by the Rusty Wind which causes all things to rust away. A suspicious looking priest visits a checkpoint all alone, yet on his back rests a bow priests wouldn't use. Meanwhile, Milo, a doctor running a clinic in the town of Imihama, is researching new medicines in secret in order to save his older sister, Pawoo, who's being corroded by the Rust. But that day a stranger appears before him...

The wanted criminal, Akaboshi Bisco, causes havoc in the town of Imihama using his bow to cause giant mushrooms to bloom. Bisco searches for a doctor who can synthesize medicine to save his mentor, Jabi, who has become gravely ill. Bisco storms into the clinic and accosts Milo, but Governor Kurokawa hears the commotion and dispatches his elite forces.

Bisco and Jabi continue their journey through Touhoku in search of Sabikui, the Rust-Eater, a mushroom said to cleanse away any rust. Milo also realizes that if he could cure his sister, Pawoo, if he had this Rust-Eater. Meanwhile, the governor of Imihama, Kurokawa, burns with an unusual obsession with killing Bisco.

On their way to Akita, Bisco and Milo pass by the sea of Calbero and arrive at a desolate town under threat from the deadly creatures, Flying Blowfish. A town that's also full of children and devoid of adults. Meanwhile, Pawoo encounters a mysterious couple living in some ruins as she pursues the others.

Bisco and Milo finally reach Konakidani when the Pipe Snake, a divine beast with two heads that's the size of a dragon, appears before them. That's also when Pawoo catches up to them with the worst possible timing. Soon enough, even Pawoo is dragged into the intense battle against the Pipe Snake. Meanwhile, Kurokawa also closes in around them...

Milo is left standing at death's door by Kurokawa's traps. Kurokawa has once again captured Jabi, and this time he shares a glimpse of his terrifying plan to utilize Tetsujin, the very same defensive weapon that covered all of Japan in the Rust Wind. It seems like no one can stop Kurokawa, and yet at the very moment Jabi feels that despair, a familiar face appears before Kurokawa...

Bisco falls into Tetsujin's reactor, taking Kurokawa down with him. The reactor begins to overload, with Milo and the others just barely escaping in time as the dome starts to collapse. However, they're given no time to grieve their loss of Bisco before their next trial assails them. With Bisco gone, Milo tries to figure out what he can do on his own now.

Tetsujin is heading for Imihama, repeatedly attacking Milo in a fierce assault. Yet just as he's about to be killed, Bisco revives from within Tetsujin. Together Bisco and Milo join forces in the final battle against Tetsujin!