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.

At Giyu Tomioka's urging, Tanjiro heads for Mt. Sagiri with his sister Nezuko who's been turned into a demon. During the night, Tanjiro catches the smell of blood from inside a temple. He enters, thinking that someone might be hurt, only to come upon a man-eating demon. When the demon attacks, Tanjiro manages to fight back with his hatchet, but the demon's strength is overwhelming. Just as the demon is about to finish him off, Tanjiro is saved by none other than.

Tanjiro is now clad in the uniform of the Demon Slayer Corps. His Nichirin Sword on his hip, and Nezuko, now awake, in a special box made by Urokodaki on his back, he heads out for his first assignment. A town to the northwest where girls have been vanishing nightly. There, Tanjiro meets Kazumi, haggard with worry after his girlfriend's been abducted. Though he does catch the scent of a demon nearby, there's just no demon in sight. Tanjiro is sure that a demon is behind this sinister incident...

The next mission is in Asakusa, Tokyo. Tanjiro is taken aback by the opulent Taisho Era cityscape, but soon picks up the demon’s scent there. His pursuit of the scent leads him to Muzan Kibutsuji. Tanjiro attempts to strike him down. But Kibutsuji transforms a passerby into demon, triggering a commotion. As Tanjiro desperately tries to get things under control, someone appears before him...

Every time Kyogai, the master of house, plays his tsuzumi, the room spins and Tanjiro struggles. Debilitated by the fractured bones he sustained in his previous battle, Tanjiro tries to fire himself up as he desperately fights on, but he is overwhelmed by Kyogai's Blood Demon Art. Will he find a way to slice off Kyogai's head?

After a desperate fight to the death, Tanjiro prevails over Kyogai. He exits the house to find Zenitsu who had escaped earlier. But it is then that he sees the strange circumstances before him... The battered Zenitsu holding the box containing Nezuko in his arms while the man in the boar's head mask stands in the way with two Nichirin Swords drawn.

Their next destination is to the north-northwest. Tanjiro and Nezuko head towards Mount Natagumo with Zenitsu and Inosuke. This mountain is covered with spider webs and is swarming with innumerable spiders. Leaving the cowering Zenitsu behind, Tanjiro and Inosuke head up the mountain where they run into fellow Demon Slayers entangled in spider webs.

As Tanjiro and the others are devoted to their rehabilitation training, the absolute master of the demons, Muzan Kibutsuji, gathers the Lower Ranks of the Twelve Kizuki. The demons, too, are preparing to make their next move. As training draws to a close, Tanjiro has improved to the point where he can fight on equal terms with Kanao. Just then, he receives word of a new mission from his Kasugai Crow.

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's group, fresh from completing their training at the Butterfly Mansion, head to their next mission, the Mugen Train. There they rendezvous with Rengoku, who arrived ahead of them. Tanjiro is overwhelmed by the always-energetic Rengoku, Zenitsu is frightened by the prospect of facing demons as usual, and Inosuke is immensely excited by the sight of the huge machine. But on this train loaded with passengers, a new battle is about to begin.

Tanjiro, Zenitsu, Inosuke and Rengoku have fallen into a deep sleep while under the control of Enmu's Blood Demon Art. As Enmu attempts to use his accomplices to destroy the spiritual cores of Tanjiro and his companions in order to defeat them, Tanjiro realizes that he is inside a dream and searches for a way to wake up. In order to awaken from the dream, Tanjiro makes a decision to use his sword to cut into his own neck.

After waking up from his dream by cutting his own neck, Tanjiro battles Enmu, who is the source of all the turmoil on the train. Enmu appears to be getting pleasure from inflicting pain on the passengers, which only infuriates Tanjiro even more. Tanjiro succeeds in severing Enmu's head, only to discover that Enmu's body is fused with the Mugen Train itself. Tanjiro is backed into a corner, but a freshly-awakened Inosuke comes to assist him and...

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.

During the fierce battle with Daki, Tanjiro continues to unleash the Hinokami Kagura, which causes a huge strain on his body. Meanwhile, Inosuke reaches the Belt Demon’s nest and saves people who have been captured. Makio, Suma, and Zenitsu, who have been freed from the belt, join in on the fight. As the ceiling of the nest is broken, Uzui appears wielding his swords.

After Nezuko attempts to attack innocent bystanders as her demon form advances, Tanjiro is finally able to make her fall asleep by singing a lullaby. Meanwhile, another demon emerges out of Daki's body after being beheaded by Uzui - Gyutaro, Daki's older brother and the other form of Upper Six. Uzui must now face both demons, Daki and Gyutaro.

An Upper Rank Demon has been defeated for the first time in a hundred years by Uzui, Tanjiro, and his comrades' effort. This news causes a ripple effect not only among the members of the Demon Slayer Corps, but also the Upper Rank Demons, who have been summoned by Muzan Kibutsuji. Meanwhile, Tanjiro is recovering at the Butterfly Mansion when he discovers that he has upset his swordsmith Haganezuka after chipping his sword and decides to head to the village where the swordsmiths live to talk to him in person.

Tokito continues advancing through the forest and finds Mr. Kanamori. As soon as they arrive at the work hut in the middle of the forest, they are welcomed by Gyokko. Meanwhile, Tanjiro continues his fight against Hantengu.

Tanjiro, Nezuko, and Genya are struggling through an arduous battle against Zohakuten and his five tree dragons. They are forced to fight defensively against the tree dragons using the four emotion demon's powers, and Tanjiro is swallowed by one of them amidst the fight. Just as Tanjiro is close to meeting his demise, Mitsuri arrives in the nick of time and rescues him. And now, Mitsuri faces off against Zohakuten to rescue the captured Nezuko and Genya...!

Tanjiro continues the fight against Hantengu. Amidst all his injuries and the Superior Four's skill, will he be able to defeat him? As the battle draws to a close, the Demon Slayer Squad must race against time to end the fight before dawn.