The story of Rurouni Kenshin takes place during the early Meiji era in Japan. It tells the story of a peaceful wanderer named Himura Kenshin, formerly known as the assassin "Hitokiri Battōsai". After participating during the Bakumatsu war, Kenshin wanders the countryside of Japan offering protection and aid to those in need as atonement for the murders he once committed as an assassin. When arriving in Tokyo in the 11th year of Meiji (1878), he meets a young woman named Kamiya Kaoru, who was in the middle of a fight with a murderer who claims to be the Hitokiri Battōsai from her swordsmanship school. Kenshin decides to help her and defeats the fake Battōsai. After discovering that Kenshin is the real Battōsai, she offers him a place to stay at her dojo as she notes Kenshin is a gentle person instead. Kenshin accepts and begins to establish lifelong relationships with many people such as Sagara Sanosuke, a former Sekihō Army member; Myōjin Yahiko, an orphan from a samurai family; and a doctor named Takani Megumi. However, he also deals with his fair share of enemies, new and old, including the former leader from the Oniwabanshū, Shinomori Aoshi and his rival from the Bakumatsu Saitō Hajime.
After several months of living in the dojo, Kenshin discovers that his successor as assassin of the shadows, Shishio Makoto, plans to conquer Japan by destroying the Meiji Government, starting with Kyoto. Feeling that his friends may be attacked by Shishio's faction, Kenshin goes to meet Shishio alone in order to defeat him. However, many of his friends, including a young Oniwabanshū named Makimachi Misao, decide to help him in his fight. He decides to accept their help and defeats Shishio in a fight, who dies in the process due to the rise in body temperature caused by his burns. The anime adapts the manga until this part, later featuring new story arcs which were not featured in the manga.
When Kenshin and his friends return to Tokyo, Kenshin finds Yukishiro Enishi, who plans to take revenge by killing his friends. At this point it is revealed that, during the Bakumatsu, Kenshin used to be married to a woman called Yukishiro Tomoe, who initially wanted to avenge the death of her fiancé, whom Kenshin had killed, but instead both fell in love and got married. It is then discovered that Tomoe was part of a group of assassins that wanted to kill Kenshin, and Tomoe is betrayed by them and captured to use as bait. Kenshin rushes in to rescue her, killing both his assailant and accidentally Tomoe, who jumps in at the last minute to save Kenshin from a fatal attack. Wanting to take revenge for the death of his sister, Enishi kidnaps Kaoru and leaves behind a tortured figure bearing a stunning resemblance of Kaoru for Kenshin to find and momentarily grieve over. Once discovering that Kaoru is alive, Kenshin and his friends set to rescue her. A battle between Kenshin and Enishi follows and when Kenshin wins, he and Kaoru return home. Five years later, Kenshin has married to Kaoru and has a son named Himura Kenji.