The Crusades. The battles that take place every 200 or so years between the Goddess Athena and Hades, the Lord of the Underworld. In an 18th century European country town, just as the Crusade is dawning, live Tenma and Alone. They have completely different personalities but are the best of friends. One day, Alone meets a woman named Pandora. From that day, the cogs of fate are set into motion.

Golden Saints gather around the Goddess Athena, in preparation for the new Crusade against the Underworld warriors. Around this time, as Tenma undergoes training to become a Saintly Warrior, he is reunited with Alone's little sister, Sasha, and learns that she has transformed into Athena. Meanwhile, thinking of his dear and far off friend Tenma, Alone feels lonely and falls into despair.