A few days before the story begins, a series of mysterious disappearances occurred at a karaoke parlor. The part-time employee Aoki Tokiya finds himself drawn into an even stranger series of events unfolding at the same location. Investigating the disappearances is Midorima, a member of a group known as the Tsukumo-shi, who has identified a suspect but cannot determine the true identity behind the incidents.

The world of Byaku Monogatari is one where human emotions can take tangible form, giving rise to supernatural entities called mononoke, or妖怪 (yokai). The Tsukumo-shi are a group of individuals who possess the power to confront and combat these manifestations. There can only ever be ninety-nine Tsukumo-shi at any given time, and the power balance among them is precariously maintained.

When Midorima guides Tokiya into becoming the one-hundredth Tsukumo-shi, the established balance is shattered. Tokiya is immediately branded a forbidden existence and becomes a target for other Tsukumo-shi who see him as a threat to the entire system. Forced to fight for his survival, Tokiya must learn to wield his newfound abilities and navigate the dangerous politics of the Tsukumo-shi while battling the mononoke that plague the city.

The narrative unfolds through several arcs. The initial arc establishes the central conflict: Tokiya reluctantly becomes a Tsukumo-shi and is immediately marked for death by his own kind. A subsequent arc involves a mysterious mass coma incident across Tokyo. Midorima falls victim to the coma while investigating, forcing Tokiya to delve into the cause alone, where he encounters another Tsukumo-shi whose allegiance remains unclear. Another noted arc traps Tokiya inside a giant insect cage, where he is attacked by a massive centipede-like mononoke and must find a way to escape without any means of calling for help. The story also prominently features the members of the real-life game-streaming group White Tails, who appear within the narrative.