The plot of School Rumble covers the daily lives of students of the fictional Yagami High School and their surroundings. The series is of the romance comedy genre, with scenes in the story being exaggerated for comedic purposes.

The heroine is Tenma Tsukamoto, a second year high school girl with no special qualities who has a crush on Oji Karasuma, a stonefaced eccentric. The generally clueless Tenma finds it difficult to confess her love to him. Complications arise with Kenji Harima, the male protagonist and a delinquent, who has developed a crush on Tenma. He too has difficulty confessing to her. The attempts of the two characters to confess their respective loves are running gags seen throughout the series.

As the series progresses, the story changes focus to the relationship that develops between Harima and Tenma's close friend, Eri Sawachika, which results from various embarrassing situations involving Eri and Harima. Harima also develops a relationship with Tenma's younger sister Yakumo Tsukamoto, who begins to assist Harima with the development and drawing of his manga.

As the story progresses, Harima gets himself into romantic situations with Tenma, the relationship between Tenma and Karasuma progresses, and Eri's and Yakumo's bonds with Harima grow stronger.