"Saint Seiya: Knights of the Zodiac" centers on a group of young warriors known as Saints, who are tasked with protecting the reincarnated goddess Athena and maintaining peace on Earth. The Saints derive their powers from constellations, which are represented by sacred armor called Cloths. The protagonist, Seiya, is the Pegasus Saint, a determined and courageous fighter who embarks on a journey to locate his missing sister. Along the way, he forms bonds with other Bronze Saints: Shiryu of the Dragon, Hyoga of the Cygnus, Shun of the Andromeda, and Ikki of the Phoenix. Each character possesses unique abilities and personal motivations tied to their constellations.

The narrative begins with Seiya earning his Pegasus Cloth by surviving a grueling trial at the Sanctuary, the headquarters of Athena's Saints. After becoming a Saint, Seiya learns that his sister, who was taken away years earlier, is being held captive by the Sanctuary's authorities. To rescue her, Seiya and his fellow Bronze Saints must confront increasingly powerful adversaries, including Silver and Gold Saints, who serve as elite guardians of the Sanctuary. The Gold Saints, in particular, are tied to the twelve zodiac constellations and represent the pinnacle of strength among Athena's warriors.

As the story progresses, the Saints uncover a conspiracy within the Sanctuary, revealing that the current Pope has been corrupted and is manipulating events to serve his own agenda. This leads to a climactic battle where Seiya and his allies must challenge the Gold Saints and ultimately confront the Pope himself. The stakes escalate further when it is revealed that the Pope is being influenced by a malevolent force tied to the god of the underworld, Hades, setting the stage for future conflicts.

The series explores themes of loyalty, sacrifice, and the struggle between good and evil, with each character facing personal trials and growth. The battles are characterized by intense combat sequences, where the Saints harness their Cosmo, an inner energy source, to unleash powerful attacks. The narrative is structured around episodic challenges and larger story arcs, culminating in a confrontation with Hades and his forces in later installments of the franchise. The series blends mythological elements with science fiction, creating a unique universe where celestial forces shape the fate of humanity.