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.

The Taurus Golden Saint Aldebaran uses his amazing strength to defeat the Specters as they attempt to close in on the Sanctuary. Then, full of hostility, Heavenly Violent Star Vennu Kagaho comes down, ready to fight. They are equally matched in this breathtaking battle, when Kagaho, affected by Aldebaran’s words, binds Aldebaran with his flames and releases a series of major attacks.

Tenma bears the full force of Asmita’s attack. When suddenly the Goldenrain reacts to Tenma’s rising cosmos and bears fruit. Asmita disappears, and Tenma and the others gather the berries and flee from the Underworld. However, even Jamir feels the evil reach of new Specters. Who should appear before them but Asmita.

Tenma and the others hear that the immortal Specters can be destroyed using berries from the Goldenrain tree that grows in the Underworld, so they quickly search for it. They reach the tree, when the Gemini Golden Saint Asmita appears. Is he friend, or foe? Asmita has been studying meditation in his own world, void of light, and so criticizes Tenma’s fighting ability, releasing the “Tenmaihourin” – which takes away a person’s five senses.

Albafica fights against Minos with all his might, releasing the “crimson zone.” However even that is deflected by the Specter’s armor, causing Albafica to finally fall. Minos then heads towards the village outside of the Sanctuary that Albafica was trying to protect. The village is destroyed, and even Agasya, a young girl mourning Albafica, is targeted by Minos.

One of the three strongest Specters, Minos, uses invisible puppet strings to invade the supposedly impenetrable Sanctuary, killing Saints off one after the other. However, a poisonous rose garden appears between Minos and the Sanctuary. Pisces Golden Saint Albafica appears in the middle of the garden. Albafica is immune to the rose’s poison, and uses his own blood to kill the Specter Niobe, however…

Though she learns of the death of Tenma, and of her brother Alone’s reincarnation as Hades, Sasha pushes away her sadness and steadfastly fulfills her role as Athena. Meanwhile, while carrying Tenma’s body, the Silver Saint Yato is visited by the Goddess Yuzuriha, who brings him to Jamir. The Chief of Jamir, Hakurei, tells him Tenma is not completely dead.

Tenma and the other Saintly Warriors head towards an Italian town where the warriors of the Underworld are gathered. Tenma realizes it is his hometown, and worries about Tenma’s fate. However, Alone appears amongst the burning ruins of the town as the reincarnation of Lord Hades. Tenma – shocked by the evil transformation of his dear friend – is mercilessly attacked by Alone

Hakurei uses a powerful attack with the help of his fallen comrades to seal Hypnos. But when he raises his blade again to destroy the barrier, King Hades appears. Tenma and Dohko come to help, but the awakened Hades is simply too powerful. But just when they think it's all over...

Hakurei goes into Hades castle alone, protected by a blade from the last Athena. He tears apart the oppossing Specters until he reaches the center of the barrier that protects Hades Castle. When he attempts to destroy it with his sword, Hypnos appears. Will Hakurei be able to defeat the foe he has hated since the last Holy War?

With the four God's barrier destroyed, Hypnos's "Barrier of Sleep" is lifted, and the forces of the Saints march on Hades castle! Hakurei gives them a rousing speech as Seiji, then enters Hades castle alone to defeat Hypnos. And as Alone paints his Lost Canvas in the depths of the Dream World, Hypnos turns him into the real King Hades...

Athena enters Sisyphus's dream. There she finds that Sisyphus torn by guilt over taking her away from Alone and Tenma. He thinks that he ruined her life, and caused the Holy War. Athena risks her life to attempt to persuade him to open his heart and rise from the darkness. But El Cid's Cosmo is finally running out in the attle with Oneiros!

Tenma and El Cid are helpless before the combined might of Oneiros and the other three Gods. But Athena appears in the dream world to save Sisyphus. Tenma and El Cid begin the fight anew to protect Athena, and succeed in removing Oneiros from the Dream World!

With one of the four gods down, El Cid finds himself confronted by Icelus. Icelus continues to overpower El Cid with his dimensional abilities, but El Cid is determined to rescue Sisyphos.

Nearing Hades's castle, Tenma suddenly finds himself standing before his undamaged village. He can't shake the feeling something is wrong as Alone and Sasha tell him everything has been a dream.

Golden Saints gather around the Goddess Athena and her Sanctuary, 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.

Hypnos gathers the four gods who control dreams. One of them, the Vision Icelus, appears in Sagittarius, avoiding Capricorn El Cid's attacks, and steals the soul of the unconscious Sisyphus. El Cid leaves the Sanctuary alone to get it back. El Cid, who had always been by Sisyphus side, felt the reason why he wouldn't wake up...

Thanatos finally gets serious after being wounded by Manigoldo. But even in the worst position imaginable, Seiji doesn't falter. Don't use the word despair so loosely, he says, and Manigoldo remembers his old days with his master and regains hope. The two use their Sekishiki Meikaiha attack in a final desperate attempt, and succeed in separating Thanatos soul from his body, but...

Manigoldo finds the location of the Twin Gods, but is helpless before the might of Thanatos, the God of Death. The Pope Seiji arrives to help him. As he struggles to withstands Thanatos’s attacks, Manigold remembers how he met Seiji when he was young. Manigoldo, a war orphan, once thought that human life was valueless… As Thanatos finally reveals his true strength, is there any way for them to win?

Tenma, Yato, and Yuzuriha are surrounded by Veronica’s zombies, only to be saved by Cancer Saint Manigoldo. Manigoldo had come to protect Tenma at the pope’s orders. With his overwhelming power, he splits Veronica’s body in two. But even this isn’t enough to kill him, and Veronica tries to cause them all to rot along with the forest. Meanwhile, the Twin Gods Hypnos and Thanatos watch the battle from the palace as they play Chess…