For several years, an undercover team known as the Mazinger Angels has operated in Japan, a group of women who pilot giant super-robots to defend the Earth from various threats. The current team is composed of Sayaka Yumi, a high school student and the pilot of the orange and white Aphrodite A; Jun Hono, a frequent part-time employee who controls the red and white Venus A; and Hikaru Makiba, a rancher's daughter who pilots the blue and white Diana A. They soon welcome a newcomer, Maria Fleed, who uses a special helmet to channel her psychokinetic powers and control the more powerful purple Minerva X after an initial misunderstanding is cleared up.

The team operates like a private investigation agency, solving crimes and incidents involving giant robots and cyborgs, with their true identities kept secret from the general public. The manga is structured as a series of mostly self-contained adventures as the Angels face a rogue's gallery of reimagined classic villains. Baron Ashura, traditionally a conjoined being, appears instead as two separate lovers, a man and a woman, who use a Mechanical Beast to commit thefts to fund their dream of buying an island together. Other returning enemies include the envious Madame Janus, the psychokinetic Archduke Gorgon, and Count Brocken, each deploying various Mechanical Beasts against the Angels.

As the Angels solve case after case, they begin to suspect a hidden mastermind is providing criminals with mecha for a sinister purpose. This figure is eventually revealed to be the mad scientist Dr. Hell, who operates from his Gool fortress and plans to take over the world. The escalating conflict culminates with the rise of the ancient Dragonsaurus, a colossal beast that once destroyed the Mu civilization. With the aid of former members of the Angel team, the four pilots manage to destroy the Dragonsaurus and finally vanquish Dr. Hell, concluding the primary narrative arc. The manga also features crossover chapters and cameo appearances from other characters created by Go Nagai, including Akira Fudo from Devilman and Honey Kisaragi from Cutie Honey.