Seikyou Private Academy, built on the intrigue of traditional occult myths, bears a dark past—for 60 years, it has been haunted by a ghost known as Yuuko, a young woman who mysteriously died in the basement of the old school building. With no memory of her life or death, Yuuko discreetly finds and heads the Paranormal Investigations Club in search of answers.

A chance meeting leads Yuuko to cling to diligent freshman Teiichi Niiya, who can see the quirky ghost, they quickly grow close, and he decides to help her. Along with Kirie Kanoe, Yuuko's relative, and the oblivious second year Momoe Okonogi, they delve deep into the infamous Seven Mysteries of the storied school.

Tasogare Otome x Amnesia tells a unique tale of students who work together to shed light on their school's paranormal happenings, all the while inching closer to the truth behind Yuuko's death.