In the Meiji Era of Japan, legend has it that the "Orochi"—an evil giant snake spirit—returns every 300 years to wreak havoc. "Yamainu," an elite fighting force, is assembled to subjugate the Orochi upon its reappearance. Presently, the squad has become involved with a secret government department conducting human experimentation using Orochi cells. This pits Yamainu leader Sousei Abeno against brothers Soramaru and Chuutarou Kumou, who stumble upon several dying escapees of the experiments.

Soramaru encounters Ageha, a criminal doctor allied with Tora, a test subject who massacred cell project researchers using abilities granted by compatible Orochi cells. Despite acknowledging their crimes, Soramaru still decides to side with the two fugitives due to his strong opposition to the exploitation of Orochi cells. With Sousei and Soramaru divided over the ethics of creating novel drugs from the essence of their immortal enemy, the only way to settle this matter may be a fight—however, Soramaru has yet to win once against Yamainu's captain.