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Akira Fudou leads the life of a typical high school student. After a chance encounter with school bullies, he is rescued by his childhood friend Ryou Asuka. Ryou and Akira catch up over the course of an afternoon that ends with them crashing a party at a nightclub. Initially uncomfortable with the environment, Akira is shocked when violence provokes some of the club's partygoers to transform into demonic monsters. He and Ryou are only saved from the encounter thanks to the intervention of a great demon known as Amon. Amon possesses Akira, and the two together form the powerful Devilman⁠—a being that, due to the influence of Akira's strong empathy for his fellow man, is resolved to keep the human race safe from the threats of demonkind.

Akira Fudo is informed by his best friend Ryou Asuka that the demons will revive and reclaim the world from the humans. As the humans do not stand a chance against the supernatural power of the demons, Ryou suggests fusing with a demon. Akira becomes Devilman, with the power of a demon and the heart of a human.

Demons exist and their power is beyond what humans can fathom. In fact they are so strong that humans do not stand a chance against them in a fight. The only thing strong enough to defeat a demon is another demon and it is through this logic that Asuka Ryou hatches the plan to have his good-hearted friend Fudou Akira possessed by a demon. If a person has a pure heart, then he might be able to control the demon that possesses him and thereby acquire power equal to that of a demon. After raising some hell in a club the plan works and Akira is possessed by the powerful demon known as Amon. Now Akira is humanity's sole champion of justice against the hidden demon menace that has plagued mankind since the dawn of time.

Akira is just another normal kid in modern-day Tokyo, until an old friend of his, Ryo, shows up and turns his world upside down. Akira learns that there is an upcoming war of demons on humanity and he has just been enlisted for a major tour of duty. But the only way to fight a demon is with their power, so Akira and Ryo risk a dangerous ceremony in an attempt to create humanity's only hope — the powerful Devilman.

Fudo Jun is a beautiful supermodel who is idolized by many. She also has a dark secret that not even she knows about at first, for within her veins run the genes that hold the next step in the evolution of mankind. The same blood as the beastlike superhumans that terrorize the city. Unlike the rest of them, though, Jun has managed to hold a tenuous grip onto her humanity, and she is recruited by the mysterious Asuka Ran, member of a secret organization within the government, aimed at controlling, if not eliminating, these berserk destroyers of mankind. Jun, as Devilman Lady, must now exterminate her own kind, but how much longer can she keep her sanity in a situation she never chose in the first place?