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.

When she was a young girl, Clare met Teresa, who said she was the strongest Claymore. To save Clare, Teresa broke the cardinal rule of the Claymores that forbids her kind from killing humans – this condemns her to death at the hands of her own kind. In time, a group of Claymores comes to kill her. Teresa can not stop the Yoma powers, and is eventually defeated and killed by a former Claymore Pricilla, who has become an "Awakened Being." Clare inherits Teresa's flesh and blood, and decides herself to become a Claymore, to avenge Teresa's death.