The story of The Empire of Corpses takes place in 19th century Europe, and revolves around John Watson. He is scouted by the government to become a secret agent- However, Watson lives in a world where “Frankensteins”- human corpses that are re-purposed with a false soul in order to use them as laborers- are used to improve industrial development.

Mushi are beings in touch with the essence of life, far more basic and pure than normal living things. Most humans are incapable of perceiving Mushi and are oblivious to their existence, but there are a few who possess the ability to see and interact with Mushi. One such person is Ginko who travels from place to place to research Mushi and aid people suffering from problems caused by them.