Naoto Hachiouji, an introverted second-year student at Kazehaya High School, prefers to avoid social interactions and draw manga in his spare time. However, first-year girl Hayase Nagatoro inadvertently discovers the manga, calls him "Senpai", and teases him to the point of crying. She frequents the Art Club room where he hangs out, and continues to bully him for his timid personality and otaku interests, sometimes in a sexually suggestive fashion, calling him lewd. As she continues to push him to become more assertive, Senpai develops a crush on Nagatoro in return, and gradually comes out of his shell and involves himself in her life.
Senpai meets Nagatoro's friends, Gamo, Yosshii and Sakura, who at first appear to be cruel and shallow high school girls who only seek to torment Senpai, but they catch on to Senpai and Nagatoro's oblivious mutual crush and they become supportive friends who scheme to bring the two closer together. The Art Club's semi-retired president Sana Sunomiya appears and tries to shut down the club, but after a contest challenge during the culture festival, allows it to continue. During the next school year, the president's younger cousin Hana Sunomiya enrolls in the high school and joins the Art Club, whereas Nagatoro joins the Judo Club. Hana quickly understands what's happening between Senpai and Nagatoro and makes her mission to help them.