The story takes place in the 18th century, two hundred fifty years before the original Saint Seiya series, during the previous Holy War between Athena and Hades. This conflict centers on three childhood friends whose intertwined destinies drive the narrative. Tenma, an aggressive but upstanding orphan, leaves his home in Italy to train at the Sanctuary in Greece, ultimately becoming the Pegasus Saint. He is reunited there with Sasha, his friend's sister, who is revealed to be the reincarnation of the goddess Athena. The third member of their group is Alone, a gentle and kind-hearted boy who loves to paint. His pure soul, however, makes him the ideal vessel for the god of the Underworld, Hades. The central conflict arises when Alone, manipulated by the mysterious Pandora, accepts his role as Hades and decides that death is the only true salvation for humanity, forcing Tenma and Sasha to oppose their beloved friend in a war that will decide the fate of the world.

Following the conclusion of this main saga, a collection of side stories titled Saint Seiya: The Lost Canvas – Meiō Shinwa Bangaihen, also known as Anecdotes, was published to further explore the universe. These narratives focus primarily on the twelve Gold Saints, the most powerful warriors of Athena, delving into their lives before, during, and after the events of the Holy War. The series is an anthology where each story arc centers on a specific Gold Saint, providing background on their training, personal struggles, and individual missions.

The first of these stories follows Albafica of Pisces, exploring his origins as an orphan raised and trained by his predecessor. It deals with the curse of the Pisces Cloth, whose roses possess deadly poison, and his internal conflict over whether to embrace his destiny or seek a cure for his poisoned blood. Another arc features Kardia of Scorpio, who, unaware that she is Athena, takes the young goddess Sasha on a journey to Mexico. There, they encounter the Jaguars, indigenous warriors who use mystical armors called Nahuals, forcing Kardia to protect Sasha from these new enemies while confronting his own fatal heart condition. A different story follows Degel of Aquarius as he receives a mysterious letter from his long-lost master Krest, a Gold Saint who has lived for over five hundred years. This leads Degel to a manor in France where a woman with an enchanting voice has been enslaving men, and he must uncover the truth of his master's disappearance. Other arcs feature Manigoldo of Cancer, who teams up with Albafica to battle a criminal organization of Black Saints in Venice, and explore the past of other Gold Saints like Sagittarius Sisyphe and Virgo Asmita. Through these standalone adventures, which often involve mythological elements beyond the main conflict with Hades, the Gaiden series enriches the characterizations of the Gold Saints, showing their friendships, their daily lives in the Sanctuary, and the personal battles they fought before the final war against Hades began.