In a world where monsters called Yoma prey on humans and live among them in disguise, humanity's only hope is a new breed of warrior known as Claymores. Half human, half monster, these silver-eyed slayers possess supernatural strength but are condemned to fight their savage impulses or lose their humanity completely.

With the balance of power broken after Isley's defeat by the ferocious Abyss Feeders, the Organization, central hub of the Claymores, deploys Alicia and Beth to the West to go after the renegade Riful. In turn, Riful continues her scheme to Awaken the remains of the powerful Rafaela. As these dire powers all finally collide, Clare and her comrades must fight for their lives in the titanic battle that ensues.