The main antagonist is the former successor of Kenshin as the Imperialists’ hitokiri, Shishio, who vows to create chaos once again in Japan because he was not able to actively take part in the Bakumatsu.
Okubo, the only living founder of the Meiji Restoration and now the head of the Interior Affairs, has been assassinated by Shishio’s subordinate, the young prodigy Soujiro. Okubo has previously confronted both Saito, a former Shinsengumi, and Kenshin, asking for their help in vanquishing Kenshin’s kohai, Shishio, who plans to wreak havoc in the newly-established government which he sees as a fraud. But before Kenshin even get a chance to give his answer to Okubo, the latter was killed.
This event prompted Kenshin to go to Kyoto and put Shishio in his place, noting that he cannot stay on the sidelines anymore with all the bad developments happening in the country.
Kaoru, Yahiko and Sanosuke were left behind in Edo (Tokyo) but the three resolved to follow Kenshin anyway, despite warnings from Saito that they will just drag Kenshin down.
Sanosuke took off on his own, vowing to train hard to be able to aid Kenshin in his inevitable battles, especially after a confrontation with Saito made him realized he will lose miserably as he only relies on his own offensive energy. On the way, he met a monk who taught him the technique Futae no Kiwami, which enabled him to pulverize an object through two quick successive hits by his right fist.
Meanwhile, Kenshin, on his way to Kyoto, met the young ninja Misao who was actually a member of the Oniwaban (a group lead by Aoshi) that he has previously encountered. They journeyed to Kyoto but an encounter with Soujiro left Kenshin with his reverse-blade sword (sakabatou) broken.
Once they reached Kyoto, Okina, former member of the Oniwaban, helped him track the swordsmith who forged the sakabatou as he was still resolved to fight using a reverse-blade sword (so as not to break his vow of not killing anyone anymore). However, they found out the swordsmith already died and his son has stopped making swords for the sake of his family. After an incident with a police spy, it was revealed that there was actually another sword left behind by his father — the principal forge of the sakabatou he gave to Kenshin before.
Afterwards, Kenshin was compelled to go to Seijuro, the one who taught him the Hiten Mitsurugi style, in order to learn the final attack that he missed before. He successfully mastered it and before parting, requested for Seijuro to protect Aoiya, the inn where Kaoru and the Oniwaban were staying at while in Kyoto, on the day of the battle with Shishio.