The series revolves around Yuto Amakawa, a seemingly ordinary teenager with a troubled past. Seven years ago, his parents died in a car accident, leaving him alone without a single relative. The only item that was left of his family is a strange and mysterious amulet which was given to him by his late grandmother. Ever since then, his childhood friend Rinko Kuzaki (and her parents[ch. 1]) has cooked for and taken care of him. His life takes a surprising turn on his 16th birthday when he meets Himari, a cat demon samurai girl. Himari reveals to him that his family and ancestors were part of the twelve Demon Slayer families that have been slaying demons since the feudal era, and that he too is a Demon Slayer. She has sworn an oath from his family to protect Yuto from the various demons that are out to kill him, but Yuto's cat allergies makes the issue much more complicated.
Later on, Yuto encounters various other girls who take a liking to him: Shizuku, a mizuchi or water deity in the form of a small child; Lizlet, a tsukumogami or artifact spirit in the form of a busty tea-serving maid; and Kuesu, another Demon Slayer who is revealed to be Yuto's fiancée and a person from Yuto's forgotten past.
As the series progresses, Yuto and the group encounter some powerful ayakashi, with some of them being allies, and Yuto eventually makes a life-changing decision to fight for his belief of coexistence between human and ayakashi.