"UFO Robo Grendizer" is a science fiction mecha anime that centers on the conflict between Earth and the forces of the Vegan Empire, an alien race seeking to conquer the planet. The protagonist, Duke Fleed, is a prince from the planet Fleed who escapes to Earth after his homeworld is destroyed by the Vegan Empire. Disguised as a human, Duke integrates into life on Earth and befriends a family of scientists, the Makimuras. He pilots the powerful robot Grendizer, a machine created by his father to combat the Vegan threat.

The Vegan Empire, led by King Gore and his generals, repeatedly sends robotic monsters and fleets to invade Earth. Duke, alongside the Makimura family and other allies, defends the planet using Grendizer's advanced weaponry and combat capabilities. The series explores themes of loyalty, sacrifice, and the struggle for peace as Duke balances his dual identity as both a human and an alien prince. Key characters include Koji Kabuto, a recurring ally from the "Mazinger" series, and Hikaru Makimura, Duke's love interest and a source of emotional support.

The narrative is structured around episodic battles against the Vegan Empire's forces, interspersed with moments of character development and interpersonal drama. Over time, the stakes escalate as the Vegans deploy increasingly powerful weapons and strategies, culminating in a climactic confrontation to determine the fate of Earth. The series blends action, science fiction, and emotional storytelling, establishing itself as a foundational work in the mecha genre.