The Smart Brain Corporation, the world's most powerful corporation, is trying to take over the world using Orphnoch, the next stage in humanity's evolution, to covertly kill off the human population. In pursuit of this, they develop three suits of power armor, called Rider Gear (Delta, Faiz, and Kaixa), to find and protect the Orphnoch King, who can fix a defect within Orphnoch DNA which causes their genetic structure to break down, leading to death. The Rider Gears are stolen by Hanagata, the Goat Orphnoch and former President of Smart Brain Corporation. He sends them to his foster children (dubbed the Ryuseiji, after the school they attended) so they can stop the Orphnoch from achieving their goal. However, Rider Gears were designed to be worn by Orphnoch, and humans are unable to activate the systems without undergoing genetic modification. A young loner, Takumi Inui, is unwillingly drawn into the conflict between the Orphnoch and humans and becomes Kamen Rider Faiz to save the life of Mari Sonada, one of the Ryuseiji. The Smart Brain Corporation begins targeting him in an attempt to retrieve the Faiz Gear. However, there is division amongst the Orphnoch, as those who wish to co-exist with humans rather than kill them, begin resisting Smart Brain, who in turn targets them as well. Most of these "renegade" Orphnochs are either killed, remain neutral or begin siding with the Ryuseiji against the Smart Brain Corporation. When the Tokyo police discover the Orphnoch are behind a series of bizarre murders, they begin operations to defeat the creatures, largely unaware of the various factions involved. They even begin performing experiments on captured Orphnoch in an attempt to find ways of destroying them, though this does not go well. The Orphnoch King eventually awakens within a young boy named Terruo, whom Naoya Kaido and Keitaro Kikuchi saved and befriended. Now, it is up to the holders of the Rider Gears to band together and fight for humanity's survival.