Thirteen members of the Sohma family are possessed by the 12 animal spirits of the Chinese Zodiac (jyūnishi in Japanese) plus the spirit of the cat who was, according to legend, left out of the Zodiac. They transform into animals when hugged by the opposite sex or when put under a great deal of emotional or physical stress (such as being sick).

The story follows the lives of an ordinary girl named Tohru and the Sohma family, as they deal with each other and a society where neither quite fits in, as well as the feared Akito Sohma, head of the Sohma family. Soon, after living with the Sohma family she began to like, then love, all of the Sohmas, and sets out to break the zodiac curse.