In the ancient city of K-to, a place modeled after Kyoto and outwardly peaceful, predatory creatures known as Youma lurk in the shadows, feeding on human victims and leaving behind a string of mysterious deaths. High school girl Miiko Kishida becomes aware of these strange incidents and soon finds herself attacked by a Youma while on a train. She is rescued by a reclusive teenage boy named Tokio Shimura, who possesses an unusual left eye. Within that eye dwells a powerful Great Youma called Catoblepas, which grants Tokio the ability to freeze time by locking eyes with anything he chooses. This power comes with a deadly risk: direct eye contact lasting five seconds is lethal due to the creature's venom, and drawing on Catoblepas's full strength forces Tokio to deepen his synchronization with it, risking his body being taken over.

Tokio is the 21st head of the Shimura family, one of four ancient guardian houses collectively known as the K-to Guardian Families. His family, designated as the Northern Guardian, resides in the Genbu Temple, a structure concealed from ordinary sight by a barrier that makes it appear abandoned. Living with him is Hakutaku, a small, robe-clad attendant whose face is covered by a talisman reading “Hakutakuzu.” Hakutaku is highly knowledgeable about Youma and sorcery, can drive a car, and is later revealed to be the physical manifestation of the temple's barrier itself, possessing immense hidden power. Miiko, whose home is next door to the temple, learns the truth about the supernatural world and, driven by curiosity and a daring personality, begins to involve herself in Tokio's battles.

The story takes place across the city of K-to, where the four guardian families maintain a network of barriers that limit Youma activity. The Southern Guardian is the Hosomi family, led by the hot-headed and skilled Suzuto Hosomi, a 21-year-old who hosts a bird-type Youma called Shinshu Kodori, granting him control over flames and flight. He operates a soba restaurant called Suzaku-an and serves as a rough but reliable older brother figure to Tokio. The Eastern Guardian is the Kuramori family, a powerful financial conglomerate known as Seiryu-kai. The current head is high school girl Michiru Kuramori, who inherits the water-controlling and healing Youma Shakara-oh from her grandmother Tamaki, a formidable elder who retains her martial prowess after passing on her power. The Western Guardian, the Byakko family, is mentioned but never appears directly in the story.

Youma are ranked on a ten-tier classification system, with lower numbers indicating greater power. Ichii is the highest class, followed by upper classes Ni through Shi, middle classes Go through Shichi, lower classes Hachi and Ku, and the lowest class Juu. The primary antagonists are the Four Fiends — Toutetsu, Kyuuki, Toutotsu, and Konton — powerful upper-class Youma serving the supreme demon Tenma Hachijun, who seeks to plunge K-to and the entire world into darkness. Tenma Hachijun has corrupted Tokio's older brother Tokito Shimura, who was originally destined to inherit the family headship. Tokito is believed to have slaughtered his parents and everyone present at his own succession ceremony, aligning himself with the Youma and becoming a key threat.

As the story unfolds, Tokio, Miiko, Suzuto, Michiru, and Tamaki confront escalating attacks from the Four Fiends, who are sent to eliminate the guardian heads. Each member of the guardian alliance faces one of the fiends in battle, with Tokio gradually learning to control Catoblepas's more dangerous abilities, including unleashing its arm to deliver devastating blows at the cost of deeper possession. It is eventually revealed that the Four Fiends are actually mere clones created by a more powerful Youma named Shikyo, a scythe-wielding figure who takes the form of a young boy. Shikyo had been hiding inside Kyuuki and emerges to challenge the guardians directly, showing interest only in opponents who can draw out the full power of their Youma.

The narrative builds toward a confrontation with Shikyo, testing Tokio’s ability to control Catoblepas without losing himself. Hakutaku also reveals its true form temporarily to aid the fight. Meanwhile, Tenma Hachijun and Tokito remain as looming threats in the background, their plans for a global takeover left as the story reaches its conclusion. After the defeat of Shikyo, the guardian families secure the city for the time being, though the larger war against the supreme demon is unresolved. The series ends with Tokio and his allies having grown stronger through their trials, the bonds between the guardians solidified, and the lingering presence of Tenma Hachijun and Tokito suggesting that the struggle to protect K-to is far from over.