Ayashi no Ceres is about a girl named Aya Mikage who leads the life of a normal high school student until she turns 16. On her 16th birthday, her own family tries to kill her and imprisons her twin brother Aki. Aya later finds out that she possesses the blood of the "tennyo" (heavenly maiden), and when severely shaken she will transform into Ceres. If left to live, she is destined to bring ruin upon the Mikage family.
The story deals with Aya's struggle to fight with her destiny and rid herself of Ceres so she can once again become a normal teenage girl. She must avoid numerous attempts on her life made by her grandfather and other members of the Mikage family, as well as find a way to win her brother back his freedom. Helping her is Suzumi Aogiri, a woman who also possesses tennyo blood, and Suzumi's brother-in-law Yuuhi, a boy Aya's age who is assigned to protect Aya. Working in the background is Aya's cousin Kagami who, keeping it a secret from the grandfather, tells the Mikage family's henchman Tooya not to kill Aya but to keep an eye on her and find out more about her powers as tennyo and Ceres.