It has been 243 years since the previous Holy War between Athena and Hades, God of the Underworld. On a tower that Roshi has been observing, the seal Athena placed ages ago has lost its effect. The spirits of the 108 Specters, Hades' soldiers, are now free. At the Sanctuary, Nachi, Ichi and Shaina notice that graves from the Saints' graveryard have been disturbed, with the bodies coming out from the inside. At the House of Aries, a shadowy figure approaches Mu, who seems familiar to him. He orders Mu to bring him Athena's head in 12 hours. When he refuses, two more figures appear. Two Gold Saints whose lives were lost in the Battle of the 12 Houses, Cancer Deathmask and Pisces Aphrodite. Since they sold their souls to Hades, he offered them new lives, bodies, and Surplices, armors from the Underworld, resembling their Gold Cloths.

The shadowy figure deduce that Mu teleported Seiya instead of destroying him. Mu blocks Deathmask and Aphrodite's paths once more and defeats them with Starlight Extinction. At Lushan's Waterfalls, Roshi tells Shunrei he is leaving and might never come back, telling her to not let Shiryu leave her side and wishing Seiya and the others would live peacefully as normal teenagers after fighting for so long. As Roshi leaves, three shadowy figures approach Shunrei. Deathmask and Aphrodite have been vanquished, but three more figures approach Mu. Shaina orders Nachi and Ichi to set fire to the remaining graves, while Jabu discovers that three more Gold Saints were revived. At Lushan, the figures ask Shunrei for the whereabouts of Shiryu and Roshi, but Shiryu, still blind, comes to her rescue.

At Hades' castle, Wyvern Rhadamanthys, one of the three judges of the Underworld, begs Pandora, a beautiful girl and Hades' representative, to give him permission to go to the Sanctuary, but she refuses, and says the revived Gold Saints will handle the mission of killing Athena. Mu heads for the House of Taurus to find Aldebaran. Shun awakens after he keeps having dreams of a girl who resembles Pandora. Sensing something is wrong, he heads towards the Sanctuary. Tatsumi, under Saori's orders, tries to keep Shun from leaving, but to no avail. Mu finds Aldebaran, but the Taurus Saint has died, and only his Gold Cloth and a small trace of his Cosmos remain. The one responsible emerges from the shadows, a Specter, Deep Niobe, who was sent by Rhadamanthys. Deathmask and Aphrodite invade Hades' Castle, hoping to see the god, but Rhadamanthys sends them to the Land of Death. Rhadamanthys appears before them and tosses them into Yomutsu Hirasaka. Niobe uses his Deep Fragrance, which killed Aldebaran, against Mu, but the Crystal Wall blocked it. Mu claims that Niobe has already died, due to Aldebaran's Great horn, only it was delayed. As Mu leaves, Niobe's body is crushed. Aldebaran's Cosmos was able to save Mu, and he claims his death was not in vain. Shun heads for a ship that will take him to Greece, but is attacked by Canis Major Sirius, Heracles Alghetti, and Musca Dio, who have revived. Shun, with his damaged Andromeda Cloth, kills all three Silver Saints with his Nebula Chain. Mu heads for the House of Gemini, but is surprised to sense two powerful Cosmos coming from it. Saga tells Camus and Shura to keep going, while he fights the new guardian of the House.

As they approach the House of Cancer, Saga, Shura and Camus can sense the presence of death, and end up in the Land of Death. Suddenly, zombies start attacking them. Shiryu finally arrives at the Sanctuary, but is attacked by someone. Saga defeats the zombies and stops the illusion with his Galaxian Explosion. Shura senses someone following them, but Saga said they will take care of them later. At the same time, Ikki appears before Shiryu, telling him to leave as they aren't allowed here, and that he's only here to observe the battle. Angered, Shiryu attacks Ikki, saying he's fighting for Athena and his friends. Ikki then points Shiryu to Seiya's direction before leaving. Shion and Dohko talk, revealing that they were the only survivors of the previous Holy War. Shiryu finds Seiya, alive, at the colisseum, due to Mu's teleportation. Even though Seiya is angry at Ikki for not joining them now, Shiryu reminds Seiya that he is their friend and comrade, and that he may be needed in this battle. Both friends head to the 12 Houses, reminiscing about the past when they last ran up those stairs to save Athena. Meanwhile, Saga and his friends are still trying to break through the House of Cancer, sensing a powerful Cosmos, belonging to Virgo Shaka, who was using an illusion to distract them for 12 hours. Saga realizes he must kill Shaka to stop the illusion and fires a powerful blast to the House of Virgo. However, Shaka protected himself with a barrier, and counters with a blast of energy, just as powerful to the House of Cancer. Shion tries to leave, sensing the attacks, but Dohko stops him, ready to settle the score.

Shion and Dohko's power clashes, but it seems Shion has the upper hand, due to Dohko's current appearance. Feeling this, Shiryu tells Seiya to go ahead while he goes to help his master. Dohko orders Shiryu to leave and attacks Shion with the One Hundred Dragons. Hyoga and Shun arrive at the Sanctuary, but Shaina stands in their way. Dohko's dragons are no match for Shion who counters with his ultimate attack, Stardust Revolution. Shiryu wears his damaged Dragon Cloth and attacks Shion. Shun understands why Saori gave the order, but he realizes they must protect her no matter what. Shaina prepares to battle Hyoga once he starts burning his Cosmo. At the House of Aries, Shion blocks the Rising Dragon, but Dohko gets up and asks Shiryu to leave. However, Shiryu can't leave, knowing his master is fighting alone. Dohko agrees to let him stay, promising to apologize to Athena later. Hyoga prepares to attack, but Shaina turns her back and allows them to move forward. Shion attacks, but the Libra Gold Cloth saves Dohko and Shiryu. Suddenly, Dohko burns his Cosmos, and reveals something amazing. His body starts to crack like a shell, and a younger body emerges from the old one. The young Libra Dohko has returned. He reveals that Athena gave him the gift of Misopethamenos, which allowed him to stay young, meaning, since 243 years passed, for Dohko, it was only 243 days. Dohko tells Shiryu to follow Mu and defeat the Specters that came to the Sanctuary. Dohko dons his Cloth after 243 years and prepares for battle. Shion and Dohko clash with their ultimate techniques, Stardust Revolution and the One Hundred Dragons. Shiryu is sent flying due to the impact. Seiya, Mu, Hyoga, Shun and Shiryu sense both Shion and Dohko's Cosmos have disappeared.

Mu arrives at the House of Cancer, destroyed by Shaka's attack. He is then bound by psychokinesis, and a group of Specters make themselves known, searching for Saga, Camus and Shura. Cyclops Gigant tries to attack Mu, but Seiya arrives in time to save him, asking Mu to let him and his friends participate in the battle. Gigant avoids his Meteors and strikes multiple blows. Then, a strange, slimy creature, who used the psychokinesis, named Papillon Myu tells Gigant and the other Specters to head for the House of Leo. Shiryu encounters Hyoga and Shun, wanting to know where his master is, but there was no trace left, so they continue on their way. Mu is freed from the psychokinesis, because Myu wants to fight him. Myu attacks with Ugly Eruption, but Mu counters with Crystal Wall and Stardust Revolution. Myu then turns into a huge insect and uses Silky Thread to bind Mu and Seiya. Shiryu, Hyoga and Shun pass the House of Cancer, not realizing their friends were trapped close by. Mu and Seiya emerged from the cocoons and find another one above them, with Myu inside. He then emerges in his ultimate form and attacks Seiya with his psychokinesis, but the voice of his friends allow him to break free, much to Myu's shock as not even Mu could do that. Mu then tells him to go to the House of Leo, while he fights Myu. Mu dodges Myu's Fairy Thronging and traps the fairies and him with Crystal Net. Myu is then killed by the Starlight Extinction. After defeating his opponent, Mu heads for the House of Leo.