Confessing to your crush is no easy task for any teenager, and it is no different for Chiyo Sakura, who was saved from being late on the first day of school at Roman Academy by Umetarou Nozaki. Touched by his action, Sakura begins to develop feelings toward him.

One fateful day in their second year of high school, Sakura finally musters up the courage to confess. Swallowing her fears, she reveals it to him in a classroom after school. However, unbeknownst to her, Nozaki is actually a praised shoujo manga artist working under the pen name of "Sakiko Yumeno." His work is acclaimed for being sensitive toward girls' feelings, but Nozaki himself has no experience with love or being in a relationship.

All this results in him misunderstanding Sakura's confession as nothing but praise from a fan, and he simply hands her his autograph. One misunderstanding leads to another, and she somehow ends up working as an assistant for his manga. Gekkan Shoujo Nozaki-kun follows Sakura as she continually tries to convey her feelings to the oblivious Nozaki while helping him with his manga, as well as meeting his quirky assistants who coincidentally also attend Roman Academy.