High school student Kazuki Muto thinks he's saving a girl from a monster, but it turns out that he's the one who needs saving! Kazuki is killed while fighting a homunculus, a malevolent creature that feeds on humans. The girl, Tokiko Tsumura, revives him by replacing his heart with an alchemical device called a kakugane. With this device Kazuki can create his own Buso Renkin, an alchemical weapon in the form of a huge lance capable of destroying homunculi.
With his new weapon in hand, Kazuki decides to join forces with Tokiko to eliminate the homunculi and destroy their master, the strange and eccentric Papillon Masked Creator!