Dormant, experimental cells begin to awaken inside their human hosts, turning them into creatures called 'Amazons'. Two Amazons- Jin Takayama and Haruka Mizusawa- transform into Kamen Riders Amazon Alpha and Amazon Omega, aiming to exterminate the growing threat.

Takeshi Hongo is a promising young man with a passion for motorcycle racing. However, his dreams are suddenly ruined when he gets kidnapped by Shocker, the evil secret organization planning to dominate the world. After being remodeled into a cyborg, Takeshi escapes and swears to protect the world from the inhuman monsters.

A man named Shoichi Tsugami has lost his memories. He doesn’t know who he is, where he came from, or how he came upon his peculiar circumstances. Tsugami, seemingly for no reason, transforms into a powerful superhuman, Agito, whenever in the presence of the beings referred by the police as the “Unknown”, a race of powerful monsters that have been causing murders around Tokyo, targeting certain people as their prey. In response, the police department unleash their newest weapon: the G3 powersuit. G3 and Agito don’t know whether they should join up and defeat the Unknowns, their common enemy, or to combat each other, keeping the mysteries that entwine them separate. Ultimately, even more mysteries unfold, with the appearance of Kamen Rider Gills, who is on a search to uncover why his father committed suicide. These mysteries and others collide, as the true nature of Agito would ultimately determine the fate of humanity.