After the evil organization Gel-Shocker was defeated, a more powerful secret society called Destron rose from its ashes to continue the quest for world domination. Shiro Kazami, a young motocross racer and college student, accidentally witnesses a murder committed by Destron, making him their next target. After several failed attempts on his life, Destron sends the mutant Scissors Jaguar to his home. Shiro arrives to find his father, mother, and younger sister murdered, and he and a young woman named Junko Tama are nearly killed before being rescued by Takeshi Hongo and Hayato Ichimonji, the original Kamen Riders known as Kamen Rider 1 and Kamen Rider 2.

Burning with a desire for revenge, Shiro begs the two Riders to transform him into a cyborg like themselves. They refuse, not wanting him to suffer the pain of losing his humanity. However, during a subsequent battle against Destron's leader, Shiro throws himself in front of a deadly laser to save the Riders, suffering fatal wounds. With no other choice, Kamen Rider 1 and Kamen Rider 2 use their own surgical equipment to rebuild Shiro as a powerful cyborg warrior. He is reborn as Kamen Rider V3, whose Double Typhoon belt grants him the skill of Rider 1 and the strength of Rider 2. In a devastating explosion caused by the Destron monster Turtle Bazooka, the original Double Riders appear to sacrifice themselves to save Tokyo, leaving V3 to carry on their legacy alone.

Shiro Kazami is a kind-hearted but tormented young man who fights to protect humanity while mourning his family. He is aided by Tobei Tachibana, a gruff but loyal mentor who also supported the previous Riders, and Junko Tama, a brave young woman who has a crush on Shiro and operates communications from a secret headquarters hidden inside Tachibana's sports shop. Junko's younger brother, Shigeru Tama, is a member of the Boys' Kamen Rider Squad, a network of children across Japan who act as scouts and messengers for V3. Shiro rides a powerful motorcycle named the Hurricane, which is equipped with its own special abilities.

The series follows a formulaic yet engaging structure as Destron unleashes a new monster each episode to execute a scheme, usually involving a specific weapon or a plan to destabilize a part of Japan. V3 initially struggles with his new powers, gradually discovering the 26 secret techniques built into his cyborg body. The early episodes are led directly by the unseen Great Leader of Destron, whose monsters are hybrid cyborgs combining animals with man-made weapons, such as Machine-Gun Snake or Hammer-Jellyfish.

The narrative evolves through several distinct arcs defined by a succession of Destron commanders. The first is Doctor G, a scientist who uses black magic and technology to create monsters, making the conflict personal against Shiro. After V3 destroys Doctor G, he is replaced by Baron Fang, a sorcerer who leads the Fang Clan and uses dark rituals and monsters based on tusked or fanged beasts. Baron Fang is succeeded by Archbishop Wing, whose monsters are all winged creatures, presenting a new aerial challenge for V3. During this time, the original Kamen Rider 1 and Kamen Rider 2 return, having survived the explosion, to assist V3 on several occasions before departing to fight Destron in other countries.

In the final major arc, a new general named Marshal Armor arrives. A Destron scientist named Joji Yuki is betrayed by Marshal Armor and has his arm destroyed. He escapes and replaces his lost limb with a powerful mechanical arm, becoming the anti-hero Riderman. Initially motivated by revenge against Marshal Armor while remaining loyal to Destron's Great Leader, Riderman clashes with and eventually allies with V3. Together, they battle Marshal Armor and his armored monsters. In a heroic sacrifice, Riderman takes control of a missile to prevent it from destroying a city, giving his life. Honoring his bravery, Shiro names him Kamen Rider 4. In the final episodes, V3 destroys Marshal Armor and confronts the Great Leader of Destron, bringing an end to the organization's reign of terror.