A young man named Keitaro Gentoga possesses a strong spiritual sensitivity that has always attracted restless spirits. A devastating encounter with a malevolent entity left his right hand cursed and forced him to become a shut-in for years. Now a university student, Keitaro tries to reintegrate into society with the encouragement of his childhood friend, Eiko Hozuki. To overcome his social anxiety, he takes a part-time job as a private tutor. His first student is Yayoi Hozuki, Eiko's young cousin.

Yayoi is no ordinary child prodigy. She is a powerful psychic medium with a unique double-pupil in each eye, allowing her to clearly see the spirit world. After a car accident that killed her father and led to her mother's soul being abducted by a powerful, embryonic evil spirit, Yayoi has dedicated herself to tracking down and capturing dangerous ghosts. Her ultimate goal is to build an army of evil spirits strong enough to confront the entity that took her mother. Recognizing Keitaro's ability to attract spirits like a beacon, she forcefully enlists his help.

The story follows the unlikely trio of Keitaro, Yayoi, and Eiko as they travel across Japan, visiting real-life infamous haunted locations. Yayoi captures malevolent spirits and seals them into dolls, using her own hair and nails as a protective counter-curse. She then forces these captured ghosts to fight and devour one another, creating a more powerful class of servile spirits she calls her "graduates." This dangerous method turns the hunt for ghosts into a dark strategic game of collecting and strengthening supernatural assets.

A major narrative arc involves the group confronting a malevolent god known as the "God of Death" or "Tai Sui," a being of immense power who has marked a new student of Keitaro's, a cheerful high school girl named Ai Kamiyo, to be his bride. This arc forces Yayoi to unleash her most dangerous graduates in a desperate battle against a divine entity. Throughout their journey, the series explores Keitaro's struggle to overcome his fear while seeking a way to remove the curse on his hand, Eiko's obsessive and borderline disturbing love for Keitaro which fuels her enthusiasm for the occult, and Yayoi's cold, pragmatic drive to recover her mother at any cost, all while the threat of the original spirit that started everything continues to grow.