After the Bakumatsu war ended in 1868, former assassin Kenshin Himura swore to defend those in need without killing them. During the transition from the samurai to the New Age, Kenshin travels through Japan with a reverse-edged sword.
When Kenshin saves the idealistic Kaoru Kamiya from the goons of Kanryuu Takeda, the strong opium drug lord who wants her school for his opium production, Kaoru invites Kenshin to stay at the school. However, Megumi Takani, a narcotics chemist, manages to flee Kanryuu and seek refuge at the school.
Meanwhile, Battosai, a serial murderer, is killing cops and putting messages on their bodies. When Kanryuu poisons the population in order to gain control of the school, Kenshin and Sanosuke Sagara, a street fighter, band together to combat their shared foe.