Seven years before the story begins, the suburban city of Mikurigaoka New Town was devastated by a bizarre catastrophe known as Fafrotskies, during which countless objects and strange beings fell from the sky. This event resulted in nearly 70,000 casualties and transformed the area into a persistent hotspot for supernatural phenomena. These phenomena are called Ghosts, reality-warping anomalies that ignore the laws of physics and common sense. In response to the ongoing crisis, the Japanese government established the Correction Bureau, an organization tasked with investigating, managing, and neutralizing Ghosts to protect the town's dwindling population of fewer than one thousand residents.

The story follows Hifumi Kagome, a second-year middle school student and a local of Mikurigaoka who serves as a Fixer, an agent authorized to use Ghost abilities to combat the threats. His life changes with the arrival of Moka Kirarazaka, a rough-mannered transfer student who is also assigned as a new Fixer. Initially clashing due to their incompatible personalities, the two are forced to become partners. To fight the Ghosts, they use specialized equipment and their own innate powers. Hifumi possesses a Primary Gear called Iron Body, which allows him to harden his flesh like steel, and a secondary weapon known as The Cut-All Blade, a toy katana that can sever any substance but only works once per sheath. Moka wields a Primary Gear named Ghost Shift, granting her the ability to turn intangible, and a Gargantuan Stomach, a seemingly normal suitcase with infinite storage capacity. She also favors a submachine gun that automatically resets its own ammunition every four seconds. They are joined by a small class of only five students, including the mechanical genius Subaru Hoshi and Jina Komatsu, whose body is slowly turning invisible due to a Ghost's influence.

As Hifumi and Moka work to "correct" reality by neutralizing Ghosts, they become entangled in a larger conflict. A giant clock within the Correction Bureau displays a countdown to the hatching of an entity known as the Lesser Cuckoo's Egg, an event that could trigger an apocalyptic-level distortion. Opposing the Fixers is the Homecoming Sect, a doomsday cult that seeks to hatch the egg, believing it will bring about one of three miracles: time travel, resurrection, or world peace. The narrative also weaves in deeper mysteries regarding the true nature of the Fafrotskies, why certain Ghosts possess world-altering power, and the secrets of their own pasts. Notably, the world of Ghost Fixers is a stealth sequel to the author's previous work, Summertime Render, as characters from that series, including the scientist Haine Minakata and the writer Ryuunosuke Nagumo, appear as authorities within the Correction Bureau, confirming that this story takes place in a future timeline following the events of the earlier manga.