It is the Taisho Period (i.e. 1912-1926). Tanjiro Kamado is living a modest but blissful life in the mountains with his family. One day, when he returns from selling charcoal in town, he finds the remains of his slaughtered family in pools of blood after a demon attack. Tanjiro rushes down the snowy mountain with the sole survivor, his sister Nezuko, on his back. But on the way, Nezuko suddenly snarls, turning on Tanjiro.

Flame Hashira Kyojuro Rengoku receives new orders: Travel to the Mugen Train, where over forty people have gone missing, and conduct an investigation. Leaving the Demon Slayer Corps Headquarters, he sets off on this new mission.

Tanjiro, Nezuko, Zenitsu and Inosuke join Rengoku on the Mugen Train. Having heard that there may be demons on the train, they are on high alert, but they find themselves falling into a slumber. Within his dream, Tanjiro is reunited with his long lost family. However, it is soon revealed that this is a trap set by Enmu (Lower One).

Nezuko, Zenitsu and Rengoku fight against Enmu to protect the passengers. Meanwhile, Tanjiro and Inosuke discover the location of Enmu's neck. They work in tandem to thwart Enmu's Blood Demon Art and sever Enmu's neck. The Mugen Train writhes in pain and derails. What will be the fate of the 200 or so passengers as well as Tanjiro and his friends?

After the Mugen Train incident, Akaza visits Muzan Kibutsuji. Guided by a crow, Tanjiro Kamado heads off to the Rengoku residence to convey Kyojuro Rengoku's last messages to his father and little brother. Tanjiro's group return to the Butterfly Mansion.

After Tanjiro visits the Rengoku residence and meets Kyojuro's younger brother, Senjuro, to deliver Kyojuro's last message, Tanjiro spends his days training and completing missions. One day, he returns to the Butterfly Mansion to find Sound Hashira, Tengen Uzui, attempting to take Aoi and Naho away on a mission against their will. Tanjiro, Zenitsu and Inosuke offer to go on that mission instead, and they head to their next destination - the Entertainment District.

After arriving at the Entertainment District, Tanjiro and his comrades infiltrate each House where Uzui's wives, Suma, Makio and Hinatsuru, work. While working as apprentices and searching for their whereabouts, Inosuke hears that Makio has been shutting herself away from everyone in her room.

After being told of Zenitsu’s disappearance and to leave the Entertainment District by Uzui, Tanjiro and Inosuke decide that they will rescue Zenitsu. That evening, Tanjiro picks up a scent of a demon, which leads him to Koinatsu Oiran being swallowed by Daki’s belt. With Uzui nowhere in sight, Tanjiro must face the Upper Six demon alone.

Enraged by Daki's contempt for human life, Tanjiro attacks her with more intensity and gradually corners the demon. But he's already gone past his physical limit. As Tanjiro collapses and all seems lost again, Nezuko appears. A vicious battle ensues and Nezuko starts transforming into a more demon-like form...