A planet called Telezart comes under attack by a race known as the Gatlantis, who wish to conquer the world and use its power for their own gain. Meanwhile, Earth and Garmillas, now allies after their ten year war, fight side by side to retake a world lost. The Yamato crew are angered by the revelation of the Andromeda class battleship. The crew receive a vision from a planet called Telezart, calling for their aid.

The newly established Earth Federal Government is enacting rapid military expansion plans culminating in the launch of four state-of-the-art Andromeda class starships equipped with Wave Motion weapons. Meanwhile, the former crew of the Yamato gathers at Captain Okita's memorial monument and try to make sense of the unease growing among them after they all received a strange vision compelling them to man the old ship.

While Kodai has difficulty coming to terms with the knowledge of what truly happened to Earth after the restoration and the possible meaning of the vision he received, Mori struggles with her own identity, her relationship and the fact that she wasn't called to the Yamato.

With unease, Kodai takes the position of acting captain of the Yamato and its crew as they prepare to launch the ship, thus rebelling against the Earth Federal Government.

The Yamato reaches the asteroid belt beyond Mars but must soon face a powerful deterrent to their rebellion in the form of the Andromeda, one of the newly launched flagships of the Earth Federation Fleet.

The Yamato comes across a survivor from a Gatlantis attack on the eleventh planet, and the crew decides to go off course from their journey to Telezart to rescue any survivors.

Trapped under rubble and deprived of sensors, the crew focuses on repairing the damage when an alarming report arrives from the outside. The Gatlantis are amassing thousands of ships in orbit around the artificial sun, and Analyzer's conclusion forces Kodai to contemplate a dramatic outcome.

Zworder, Emperor of the Gatlantis, appears in front of Kodai and forces a dilemma.

The continued search for the planet Telezart leads the Yamato through a strange spatial phenomenon.

An adversary from Kodai’s past forces the Yamato into a dangerous game of cat and mouse.

The crew of the Yamato are in dire straits when a supposed onboard spy compromises their location.

The crew’s hard-fought journey to reach Telezart comes to a head. With heavy enemy presence in the area, Yamato is driven into a corner, and available options are dwindling.

Yamato works under fire to break up the rocky crust imprisoning the planet Terezart, while Cosmo Marines and fighter pilots fight against Gatlantis' massively armed ground forces. Kodai, Sanada, and Saito venture under the surface of Terezart to meet the goddess Teresa.

Teresa reads through Desslers mind, dredging up old memories from a time long passed. Kodai sneaks up behind him, intent on ending him for good. Keyman arrives minutes later, wanting to find out the truth. It is revealed that he himself is a Dessler, and nephew to Albelt Dessler. Keyman turns his gun on Kodai and knocks him unconscious.

Keyman finds himself questioning his choices, and goes back to Teresa to seek guidance. Albelt also finds that he himself requires answers, and also seeks Teresa's counsel, even if he does not necessarily want it. Keyman, now having a new purpose, frees the captives aboard Dessler's ship and flees back to the Yamato.

Gatlantis have begun their second phase of invading the Solar System, by sending an advanced force to Saturn. The UNCF fleet moves to defend Saturn, but are slowly overwhelmed. On Earth, the President of Terra declares open war with Gatlantis. Admiral Yamanami, in charge of Andromeda, takes his fleets and counter-attacks against Gatlantis.

Just as Gatlantis prepares to slaughter the Terran fleet, Wave Motion Gun shots crash through Saturn's rings and destroy a portion of the Gatlantis fleet. Terran ships jump through the rocks and begin their assault, as more de-warp into the system. Before the fleets can fight for too long, the White Comet jumps into Saturn and destroys a chunk of it. The Wave Motion fleet scattered, the Yamato attempts to use the Wave Motion Gun to disable the White Comet, but are instead knocked out of commission and dragged into the white abyss.

The Space Battleship Ginga, a Yamato class battleship, begins counter-attack operations against Gatlantis. Gatlantis attempt to thwart Ginga and her fleet, but are ultimately wiped out. Meanwhile, Yamato has crashed on a world within the White Comet, and the crew are exploring the ancient ruins on the planet.

Kodai and Keyman have departed Yamato in search for answers. They stumble across ancient ruins, in which an old AI is guarding vital information about Gatlantis. The AI takes over Analyzers body, and wishes to speak to the last human of this world. They take the AI to Toko Katsuragi, the Gatlantis spy, who is pure blood. Elsewhere, Zwordar orders the White Comet to warp to Mars Defence Line.

Katsuragi tells the AI to reveal everything about the planet, and Gatlantis. It is revealed to Kodai and the crew that Gatlantis are artificial, and that they have a major kill switch right under their leaders feet. Zwordar orders the planet Yamato is on to be destroyed. At the Mars Defence Line, Admiral Yamanami with an upgraded Andromeda, fights through hordes of enemy ships in an attempt to reach the centre of the White Comet. He sees that Yamato is alive, and using his ship as a sacrifice, rescues Yamato.

The Yamato receives repairs and upgrades at the shipyard above Mars, where much of Ginga's parts are transferred over. Repaired, the Yamato sets out to chase after the White Comet and end the war once and for all. However, before the Yamato can get far, she is attacked by Dessler, who struck a deal with Gatlantis. Kodai orders the Yamato to warp into Desslers ships bow, where they can board and disable the ship.

Keyman and Dessler face off on the bridge. The Gatlantis envoy attempts to force Keyman to kill Dessler, so he can see their emotions. Kodai arrives on the scene and attempts to stop the conflict, and is nearly shot dead for it. Yuki, who had been tailing Kodai, leaps out from behind cover and takes his bullet. The grief overwhelming, the Gatlantis envoy plans to stand down until a guard executes him. Dessler bids Yamato a farewell, and leaves the area for good. Meanwhile, Gatlantis has jumped ahead and has begun to invade Earth.

The Yamato warps to Earth, just ahead of the White Comet. Using Dessler's ship as a shield, they fire the Transit Wave Motion Gun, which destroys the protective layers surrounding the Gatlantis homeworld. Garmillas warps in to defend the planet while the Yamato sneaks on ahead. Yamato charges through the White Comet, becoming heavily damaged. The fighter squadron make it a bit further, and head to the throne room, where they come face to face with Zwordar.

Zwordar activates Golem, which wipes out the Gatlantis race, all but himself. He is absorbed into the Ark of Destruction, which begins to transform. The Yamato manages to escape the area, but the gravity anchor is holding them. Keyman, using a Wave Motion torpedo, sacrifices himself to free Yamato. Too damaged to continue, the Yamato is evacuated. Using the now bleeding core of the Yamato, Kodai, as well as Yuki, use the Yamato to destroy what remains of the Ark of Destruction, ending the war.

Six months have passed since the Gatlantis war. The surviving Yamato crew are at Heroes Hill, mourning their lost comrades. In the Time Fault Factory, the Yamato warps out from a higher dimension. Kodai and Yuki are alive, but trapped in this higher dimension. Yamanami, Sanada, and a few others attempt to convince the Earth Council to let them use the Time Fault as a booster, to save Kodai and Yuki. It's put to a vote, and the Yamato Crew win unanimously. Yamato is boosted to the higher dimension, and Kodai and Yuki are rescued. The Yamato returns to real-space and returns to Earth.