Genius biochemist and champion motorcyclist Takeshi Hongo is kidnapped by Shocker, a secret terrorist organization composed of remaining Nazi elements seeking world domination. At their hidden laboratory, he is surgically transformed into a powerful cyborg with grasshopper DNA, designed to become an obedient super-soldier. Before Shocker can complete the brainwashing process, a sympathetic scientist named Professor Midorikawa helps him escape at the cost of his own life. Now possessing incredible strength and the ability to transform using the wind-powered belt fused to his body, Hongo adopts a grasshopper-themed helmet and motorcycle to fight back as Kamen Rider, though he constantly wrestles with whether his cyborg body still makes him human.

The series is set in 1970s Japan, where Shocker operates through elaborate schemes involving hybrid monsters known as Kaijin, each combining human and animal or plant traits. These creatures include Spider Man, Bat Man, praying mantis, jellyfish, and dinosaur hybrids, among many others, with Shocker plotting everything from human experimentation and child kidnapping to constructing cobalt bombs and destroying Tokyo. Hongo is joined in his mission by FBI agent Kazuya Taki, who investigates the organization, and motorcycle team manager Tobei Tachibana, who provides support and mentorship.

During the filming of episode ten, actor Hiroshi Fujioka broke his leg performing his own motorcycle stunts, forcing a major narrative shift. To cover his absence, the show introduced freelance photographer Hayato Ichimonji, another Shocker victim whom Hongo rescues before brainwashing. Hayato becomes Kamen Rider 2, possessing a similar belt that requires a verbal transformation command, marking the first use of the series iconic Henshin shout. Hongo departs to battle Shocker overseas while Hayato protects Japan, though Hongo returns later in the series, and the two fight together as the Double Riders.

After many battles, Shocker is defeated but its leader survives, reforming the organization into the more dangerous Gel Shocker. This new group creates hybrid monsters combining two animal traits with a human base, such as crab-bat and jellyfish-wolf hybrids. The series culminates in a final confrontation where the Double Riders destroy Gel Shockers base, apparently killing its leader, though his survival remains ambiguous. The supporting character Ruriko Midorikawa, Professor Midorikawa daughter who initially blamed Hongo for her father death, eventually joins him overseas and does not return, while Taki leaves Japan for America. Hongo returns to university where he mentors a young man named Shiro Kazami, who would become Kamen Rider V3 in the subsequent series, while Hayato continues his fight against evil.