In Settsu Mine, Hyōgo Prefecture, Saitō Hajime leads the Japanese police in tracking Shishio Makoto, a notorious renegade who was betrayed by the government after helping them defeat the Tokugawa shogunate during the Battle of Toba–Fushimi. However, Shishio's men ambush and massacre the police in the mine; Shishio tells Saitō his plan to conquer Japan before leaving.
After the events of the first film, Kenshin Himura continues to live in the kenjutsu dojo of Kamiya Kaoru alongside Yahiko Myojin, Sanosuke Sagara, and Megumi Takani. He is called by a government official to track down Shishio, who is terrorizing Kyoto and its surroundings. Though he declines the request at first, he relents when the official is murdered by Sōjiro Seta, Shishio's capable underling. Just after Kenshin's departure, an enigmatic figure arrives in Tokyo and searches for him, beating Sanosuke Sagara along the way.
On the road, Kenshin meets Makimachi Misao, who attempts to steal his sakabato. While the two converse, they are alerted by a boy to the plight of his parents and brother, all of whom are killed by Shishio's men for trying to report their atrocities to the authorities. Kenshin defeats Shishio's men, though his identity as Hitokiri Battōsai is revealed. Kenshin is taken to Shishio himself, the latter ordering Sōjiro Seta to duel Kenshin, which ends with Sōjiro breaking Kenshin's sakabato. As he leaves the scene, Kenshin urges the villagers, including the orphaned boy, not to take their revenge against Shishio's men.
Arriving at Kyoto, Kenshin is asked by Misao, who is impressed by his words, to take shelter at an inn run by Kashiwazaki Nenji, actually a semi-retired ninja called Okina once employed by the Tokugawa shogunate known as the Oniwabanshu who were previously employed by the Tokugawa shogunate; Misao herself is also an aspiring ninja. Okina warns Kenshin that a lieutenant of his, Shinomori Aoshi, has made it his life goal to kill the strongest man in Japan - Kenshin.
Meanwhile, Kaoru decides to follow Kenshin to Kyoto, accompanied by Yahiko and Sanosuke. At the same time, Kenshin discovers to his dismay that the person who made his sakabato, Arai Shakku, has died years before. His son, Seiku Arai, initially refuses Kenshin's plea for another sakabato, but when Shishio's elite warrior, Sawagejō Chō, kidnaps his baby, Seiku asks Kenshin to defeat him. Seiku gives him a twin of the previous sakabato, which Kenshin uses to defeat Chō. By interrogating Chō, the government learns that Shishio plans to raze Kyoto to the ground that night. The government police, together with the Oniwabanshu ninja, and the newly-arrived Kaoru, Yahiko, and Sanosuke, battle Shishio's men, while to prevent Aoshi from interfering Kenshin, Okina challenges his former pupil into a duel, which ends in his defeat. However, Kenshin realizes that Shishio's main goal is to set fire not to Kyoto, but Tokyo.
Kenshin discovers Shishio's ship about to set sail to the capital after learning that Sōjiro has kidnapped Kaoru. There, he has an inconclusive battle with Shishio, which ends when Kaoru is thrown over board. Kenshin jumps into the sea, but is unable to locate her. The film ends with a mysterious man finding Kenshin's unconscious body washed up on the beach and carrying him away.
Key figures and their allies weave through a cityscape of shifting loyalties, secretive orders, and a harsh question: how far will a man go to rebuild a nation in a world where the old order is falling apart?
