Ryouko Otonashi is a cheerful and frivolous student at Hope's Peak Academy, an elite school that accepts only the most talented students. However, Ryouko is different from the others: as a chronic amnesiac, she tends to forget events and faces, recording everything she witnesses in a notebook that can be trusted when her memory cannot be. In addition, her irritable childhood friend, the "Super High School-Level Neurologist" Yasuke Matsuda, works tirelessly to cure her disorder. Yasuke is the only person whom Ryouko can never forget—after all, she is deeply in love with him.

This awkward pair lead a hectic but happy life at Hope's Peak Academy—until they are confronted by a strange girl who seems to be the very embodiment of despair. As her notebook becomes increasingly unreliable and Yasuke's dark secrets are revealed, can Ryouko cling to hope, or will she give in to despair?