Kagome Higurashi is a modern day young girl who lives with her family by the old Higure shrine. Unbeknownst to Kagome, she is the reincarnation of priestess Kikyo and posseses the "Jewel of Four Souls" (the Shikon jewel). One ill-fated day, Kagome locates an ancient well near her home and is abruptly transported through the well and into a feudal Japan, inhabited by demons. There, she encounters Inuyasha, son of a powerful demon father and a human mother, who is pinned to a tree by an enchanted arrow.

When a shapeshifting demon with a thirst for human flesh, known as "youma," arrives in Raki's village, a lone woman with silver eyes walks into town with only a sword upon her back. She is a "Claymore," a being manufactured as half-human and half-youma, for the express purpose of exterminating these monsters. After Raki's family is killed, the Claymore saves his life, but he is subsequently banished from his home. With nowhere else to go, Raki finds the Claymore, known as Clare, and decides to follow her on her journeys. As the pair travel from town to town, defeating youma along the way, more about Clare's organization and her fellow warriors comes to light. With every town cleansed and every demon destroyed, they come closer to the youma on which Clare has sought vengeance ever since she chose to become a Claymore.