A monster appears during the industrial revolution and infects humans with its bite, turning them into Kabane. Kabane are aggressive, undead creatures that cannot be defeated unless the glowing heart, which is protected by a layer of iron, is pierced. Unfortunately, most melee weapons and the steam presssure guns used by the Bushi are not very effective against them. On the island Hinomoto, people have built fortress-like stations to shelter themselves from these creatures. People access the stations and transport wares between them with the help of Hayajiro, armored locomotives running on steam. One day a Hayajiro under the control of the Kabane crashes into Aragane station and they attack the city. A young engineer called Ikoma uses the opportunity to test with success his anti-Kabane weapon, the piercing gun (ツラヌキ筒tsuranuki zutsu?), but is infected in the process, although he manages to resist the virus and become a Kabaneri, a human-Kabane hybrid. Assisted by Mumei, another Kabaneri who appears to help them, Ikoma and the other survivors of the station board the Hayajiro Kotetsujyo (甲鉄城Kōtetsujō?, Iron Fortress) and depart to seek shelter elsewhere, fighting the hordes of Kabane along the way.