Miko is a typical high school student whose life turns upside down when she suddenly starts to see gruesome and hideous monsters. Despite being completely terrified, Miko carries on with her daily life, pretending not to notice the horrors that surround her. She must endure the fear in order to keep herself and her friend Hana out of danger, even if that means coming face to face with the absolute worst. Blending both comedy and horror, Mieruko-chan tells the story of a girl who tries to deal with the paranormal by acting indifferent toward it. [Written by MAL Rewrite]

For many years following the North Ambrian Disaster, North Ambria has been known as the poorest region in Zemuria. After the state suffered a major loss due to the mysterious Salt Pale turning citizens and buildings into salt, the economy has never truly recovered. Out of necessity to secure foreign investment for the state, the former state military has turned into a group of mercenaries known as the Northern Jaegers. Wishing to join the largest group of mercenaries on the continent, Lavian "Lavi" Winslet, a promising rookie, enlists with the Northern Jaegers. Although she has only been with them for half a year, the reserved but capable Lavi Winslet is well respected by her peers. When Lavi and her team are tasked with gathering information regarding the Imperial Hero of Erebonia—a new threat to the state—she discovers that there may be more to the continent's intricate politics than meets the eye.

The story takes place shortly before Cartaphilus took a nap and Chise became an auditor at the academy. Elias and his friends help Chise prepare for the academy, where in the middle of everyday life, Spriggan visits the mansion on a spooky horse with the words, "The appearance of the ghost hunting association is unusual this time." Gabriel, an ordinary boy who just moved from London, was bored of his environment of parting with friends, being in an unfamiliar location, and everything else. Sitting by the window and glancing beyond, he spotted a purple smoke and decided to chase after it, looking to escape his boredom. Though it should not, the world of the boy begins to converge with the wizards, who live on the other side behind a thick veil.

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.