Camouflaged as ordinary people, homunculi roam the globe hunting unsuspecting civilians. They were forged centuries ago by European alchemists and can only be vanquished with weapons called Kurogane. Every Kurogane is molded to the instincts of its bearer, manifesting as a distinct power known as a Busou Renkin.
One afternoon while returning home from school, Kazuki Mutou witnesses a helpless girl besieged by a homunculus. When he tries to step in, the girl instead saves his life, breaking his naive assumptions. She introduces herself as Tokiko Tsumura, and Kazuki soon discovers that she has inadvertently embedded a Kurogane within him. Now thrust into the battle against homunculi, Kazuki must abandon his former carefree existence to safeguard those he loves. He realizes that every choice now carries weight, and the stakes are higher than he ever imagined.