A teenage boy named Gorou, whose shallow ambition is to become popular with girls, finds his life irrevocably changed when he saves a girl named Shichiha from drowning in a river. This encounter initiates a strange and supernatural relationship, as Shichiha possesses a unique and grim power. She can take the place of someone who has died, becoming the victim in their stead. This ability is immediately put to the test when Gorou himself is murdered, and Shichiha uses her power to replace his death.

The central conflict of Shichiha Gojūroku is Gorou's desperate quest to investigate and solve the mystery of his own murder. With Shichiha having sacrificed herself to temporarily undo his death, he is given a second chance to uncover the identity of his killer. The narrative follows a specific arc once the culprit is found: supernatural forces act to make the perpetrator become the victim of their own crime, resetting the balance. As Gorou attempts to navigate this deadly puzzle, he carries a personal book of things he wants to accomplish before dying, a plot device that hints at a pre-existing illness or fatalistic outlook that motivates his actions. The story blends elements of mystery and the supernatural with shōnen-style action sequences.

The main characters are defined by their contrasting roles in this supernatural cycle. Gorou is impulsive, somewhat foolish, and motivated by a desire for fame, though he reveals a more determined side when forced to confront death. Shichiha is the mysterious female lead whose supernatural abilities are central to the plot, though she often lacks agency in the developing relationship. The supporting cast includes generic side characters and a childhood friend of Gorou, but the narrative primarily focuses on the central pair solving supernatural murder cases that arise around them. The plot is structured as a series of mystery cases. In one notable arc, the main characters investigate a gruesome scene in a school, a narrative that has been criticized for having characters act illogically, such as seeking out a drugged and unconscious Gorou rather than calling for adult authority.