The 16-year-old Kisaragi Honey is not your typical Japanese teenager. She has a penchant for getting into trouble and being both naughty and nice. One day her carefree life is suddenly rocked when she receives an odd message from her father. Rushing to his laboratory, Honey finds her father murdered. The perpetrators are agents of the evil organization called Panther Claw. They are after Prof. Kisaragi's invention — the Air Matter Transmutation System. Honey fights off Panther Claw and finds the consciousness of her father alive within a robot facsimile.

Prof. Kisaragi shockingly reveals to Honey that she is herself a cyborg which he had created, having built her to be the perfect android, capable of human emotion as well as independent thought. To this end he had raised her as he would a human daughter. The professor had also placed the Air Matter Transmutation System into her body. Using its powers, Honey is able to change into different personae, the most powerful of which is the spicy redhead "Cutey" Honey.

Honey vows to avenge her father's death and wages a personal war against Panther Claw. She is aided (hampered) in her battles by the Hayami Clan consisting of brothers Seiji and Junpei, and their perpetually "horny" father, Danbei.

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Sequel: Shin Cutie Honey
Alternative version: Cutie Honey Flash
Alternative version: Re:Cutie Honey