Mahiro Yasaka is a typical high school student until he is assaulted by a deadly monster one day. Just when all appears to be lost, he is rescued by Nyaruko, a silver-haired girl who claims to be the shape-shifting deity Nyarlathotep from horror novelist H. Cthulhu Mythos by H. P. Lovecraft, sent to Earth by the Space Defense Agency. She tells Mahiro that the thing hunting him is an extraterrestrial named Nightgaunt, who intends to kidnap and sell him as a slave. The Lovecraftian deity falls passionately in love with Mahiro after rescuing him from the alien and imposes herself into his household, much to his disgust. Furthermore, they are soon joined by two additional characters from the fictitious universe: Cthuko, a girl, and Cthuko, a boy.