A plague-like wind blows across the arid, sandy expanse of a post-apocalyptic Japan. As it sweeps over the living and nonliving alike, rust is all that remains in its wake. The cause of the catastrophic state of the world is believed to be mushroom spores. Bisco Akaboshi, known as the "Man-Eating Mushroom," is a wanted criminal archer whose arrows instantly grow mushrooms wherever they land. However, he is in truth a "Mushroom Protector," a person who spreads fungi in order to enrich the land and return it to its previous state. Alongside the crab Akutagawa and young doctor Milo Nekoyanagi, Bisco ventures through the wastelands of Japan searching for the legendary "Sabikui"—a panacean mushroom said to devour all forms of rust.

Seven Japanese high school students enjoy international renown for their remarkable talents. One day, these friends survive a plane crash only to find themselves in the medieval fantasy world of Freyjagard, where two human races live side by side in a feudal society: the byuma, who have animal features and formidable strength, and the hyuma, who have a small chance of magical aptitude. After being rescued by the byuma Winona and her adopted elven daughter Lyrule, the group pledges to use their advanced skills and knowledge to pay back the people of Elm Village for their hospitality and find a way to return back home. Tsukasa Mikogami, the prime minister of Japan, acts as the leader of these young geniuses and organizes their efforts to intervene in Freyjagard and gather the information and resources necessary for achieving their goals. Believing that there is a connection between their current situation and an ancient legend about seven heroes from another world who defeated an evil dragon, Tsukasa directs the others to learn about the culture around them and search for any clues leading them back to Earth. But he also gives another instruction: to take it nice and easy, lest they ruin this world by giving it their all.

Noel longs to be a Seeker like his heroic grandfather, slaying the beasts that emerge from Abysses and exploring far-off lands. Unfortunately, it turns out he's nothing but a measly Talker–a job with no combat skills whatsoever. Undaunted, Noel sets out to establish the strongest clan in all the land, using his silver-tongued Talker skills to unite assassins and heroes under his leadership.

After succeeding in their winter conflict against Taiju Shiba and his Black Dragons, the Tokyo Manji Gang absorbs their group's remaining members. Due to his heroic courage and indomitable spirit, Takemichi Hanagaki should have accomplished his goal of defeating the tragic fate awaiting his girlfriend, Hinata Tachibana. In reality, Takemichi's troubles are far from over. Although Takemichi's actions have exposed Tetta Kisaki's treachery, the conniving schemer has found power elsewhere: Tenjiku, a dangerous gang led by the enigmatic Izana Kurokawa. Izana sets his sights on Manjirou "Mikey" Sano, pursuing a vicious interest in the Tokyo Manji Gang's aloof leader. In the future, Takemichi discovers that the machinations of Izana and Kisaki led to Mikey's moral ruin—a downfall that directly results in Hinata's death. Unfortunately, a terrible loss robs Takemichi of his time-leaping ability, stranding him in the past with one final chance to rescue everyone he loves.