A marine scientist named Keisuke Jin returns to Tokyo after six months away, only to be immediately targeted by operatives of G.O.D., the Government of Darkness, a secret terrorist organization bent on Japan's destruction. After surviving the initial attack, he reunites with his father, Keitaro, a brilliant robotics scientist, and his fiancée Ryoko. G.O.D. attacks again to steal Keitaro's technology, fatally wounding both father and son. With his last breath, Keitaro performs emergency surgery, transforming the dying Keisuke into a Kaizorg, a powerful cyborg designed for deep-sea exploration, who becomes the Kamen Rider X. Ryoko is revealed to be a G.O.D. agent, though her true motives become complicated with the sudden appearance of her mysterious identical twin sister Kiriko.

The newly born X-Rider struggles with the loss of his humanity while seeking revenge against G.O.D. and understanding Ryoko's betrayal. He is initially aided by a copy of his father's mind housed in an underwater sea base, but his father's program self-destructs almost immediately to force Keisuke to become independent. The early storylines also focus heavily on the twin sisters, who are revealed to be Interpol agents investigating G.O.D., but both meet tragic ends within the first several episodes.

Keisuke eventually connects with Tobei Tachibana, the veteran mentor of previous Kamen Riders, who operates a coffee shop that becomes a new base of operations. The series follows a two-part structure. For the first 21 episodes, Keisuke battles monsters based on figures from Greek and Roman mythology. His primary recurring nemesis during this period is Apollo Geist, G.O.D.'s flamboyant and powerful Chief of Security who wears a white tuxedo in his human guise. Their rivalry spans over a dozen episodes, with Apollo Geist being destroyed, revived in an enhanced form, and finally defeated for good.

Following Apollo Geist's final defeat, the series enters its second half as the giant robot King Dark assumes command of G.O.D. Under King Dark, the organization deploys a Villain Corps of monsters that are bizarre combinations of animals and historical or fictional figures, such as Ant Capone and the infamous Starfish Hitler. The narrative becomes more serialized as Keisuke and G.O.D. race to collect fragments of a powerful machine's blueprint. Kamen Rider X receives a power upgrade during this period with the help of Kamen Rider V3, changing his transformation cry from Set Up to Dai Henshin. Previous Riders including Kamen Riders 1, 2, V3, and Riderman appear in later episodes and the theatrical film to assist X-Rider in the final battles against King Dark. The climax reveals that King Dark is controlled by Dr. Noroi, a former colleague of Keisuke's father, whom Keisuke defeats before riding off into the sunset.