The story begins when high school student Mutou Kazuki is killed one night saving a mysterious girl from a monster, only to wake up and find it was only a dream. However, he soon finds out how real that dream was when a giant serpentine monster attacks him and his sister. Tsumura Tokiko, the girl from his dream, explains that the monster is a homunculus. Kazuki had been attacked and killed by it when rescuing Tokiko, however the girl revived him by placing a kakugane medal in his chest.
The kakugane, Tokiko explains, is an alchemical device that when activated can give him the power to fight homunculi. Using this, Kazuki creates his own Arms Alchemy (busou renkin), an alchemic weapon in the form of a huge lance. Along with Tokiko and her own Arms Alchemy (busou renkin), Kazuki joins the fight against the homunculi and their master.