The story follows Tachibana Misaki, a 15-year-old girl who's bullied at school. In her quest to become stronger, she decides to enter the delinquent path, aiming for a shinny tomorrow.

The series began as a fairly humorous and lighthearted satire of Japan's teenage delinquent-gang subculture told from the perspective of Matsushita Tadashi (who also narrates these early Karate Bu stories), a 2nd year student at Kangokou High and a constant target of Kangokou's numerous bullies who beat him up routinely after school. He is almost always accompanied by his best friend Saitou Takaki, who is also constantly harassed. As the pair grow increasingly tired of being victimized they decide to join the titular Karate Club, which is notorious throughout Osaka's youth gangs for training and producing the city's most hardened and toughest teenage thugs while maintaining the facade of a legit school sports club. But when they join the club, they find themselves picked on just as much if not worse by the club's current members. But as the story progresses they grow to be increasingly capable fighters.

As the series went on it gradually changed its tone to a more serious and violent martial arts manga, with the narrative shifting from the perspective of Matsushita to Takagi Yoshiyuki, the smart mouthed, tough-as-nails captain of the Kangokou Karate Club.

Along with the manga's change in attitude and central character, the various teenage fighters throughout the series grew increasingly stronger and even began to tap into superhuman ki abilities, putting Osu!! Karate Bu in the company of other similar epic Shōnen fighting manga such as Yu Yu Hakusho, Dragon Ball, and Fist of the North Star.

Osu!! Karate Bu was wildly popular in its native Japan, but is otherwise almost completely unknown in most other countries. It spawned a four episode OVA mini-series released over a period of two years from 1990-1992, a 1990 live action movie, and a 1994 Super Famicom fighting game.