Thankfully, the Earth receives assistance from Starsha, who hails from the planet of Iscandar. She sends her two sisters to Earth with the means to travel to her planet: the first, Yurisha, delivers plans for the Wave Motion Engine. Earth's navy must fight off the Garmillans to secure safe passage for the second visitor, Sasha. In the battle, known as Operation M, Captain Juzo Okita manages to fend off the Garmillans long enough for Sasha to reach Mars with the Wave Motion Core, although Sasha dies in the crash landing. Most of the ships sent to accompany Okita are sunk, including the Yukikaze, captained by Mamoru Kodai.
A few months later, Mamoru's younger brother, Susumu, overhears a conversation that suggests Operation M was a diversionary tactic. Susumu, who helped deliver the Wave Motion Core from Mars, confronts Okita, who is recovering in a hospital from injuries sustained during the battle. He expresses remorse for Mamoru's death.
Afterwards, while looking at a prototype Cosmo Zero fighter, word reaches Kodai and his friend, Daisuke Shima, of a Garmillan carrier reaching earth. Kodai and Shima commandeer the Cosmo Zero to shoot down the carrier, but end up crash-landing near the Garmillans' apparent target: the derelict remains of a 20th century cruiser...
Kodai and Shima are assigned to the ship as Tactical Officer and Navigation Officer, respectively. Although both are fresh from the academy, they were brought on as a result of most of the other selected crew for the Yamato dying during the Garmillans' last attack, in addition to the previous candidate for Tactical Officer, Mamoru Kodai, dying during Operation M.
The Garmillans attack the Yamato again as it tries to lift off. Thankfully, with the aid of other world powers lending precious energy to the Yamato to activate its Wave Motion Engine, it is able to escape the Garmillans' attack and make way for Iscandar.
Raleta, the commander of the forward base, orders ships dispatched to sink the Yamato. The Yamato fends off the fighters and lifts off from the floating continent. With that, Okita orders a test-firing of the Yamato's secret weapon: the Wave-Motion Gun. The test firing is more successful than anyone could have realized: while only meaning to destroy the forward base, the Wave Motion Gun ultimately vaporizes the floating continent. Weapons Officer Yasuo Nanbu is excited at the power of the weapon, believing the Yamato could single-handedly fight against Garmillas. Okita, however, insists the Wave Motion Gun only be used for self-defense.
An away team consisting of Kodai, Communications Officer Yuki Mori, Field Medic Makoto Harada, and a robot dubbed Analyzer, find that the signal originates from an Earth ship. While investigating, both the Yamato and the away team are ambushed. The Yamato fends off the tanks attacking it, while Kodai and the away team fend off the automated soldiers sent by Garmillas. Kodai picks up an old sidearm in the ship during the scuffle, then later discovers that it had belonged to his brother, Mamoru. To his shock, the ship sending the distress call was the Yukikaze, the ship Mamoru captained. With the fate of Mamoru still a mystery, Susumu leaves a grave marker for the Yukikaze and its crew at the ship's crash site before the Yamato departs.
In preparation for the assault on Pluto, Kodai transfers Rei Yamamoto, an accountant on the Yamato, to the fighter squadron (in spite of the squad leader Saburu Kato's reservations). While the fighters are scouting ahead, however, the Yamato falls under attack from the Pluto base's weapon: an energy cannon that uses an array of orbiting satellite relays to direct the beam fired from the cannon. This allows Schulz to attack the Yamato from virtually any direction, forcing the ship to crash-land on Pluto and sinking it beneath the planet's frozen oceans...
Eventually, the line-crossing ceremony ends as the Yamato leaves the heliosphere. The last call made before this is from Niimi, but it is not to her family: it is to General Kotetsu Serizawa of the UN, who tells her that she is humanity's last hope...
As the Yamato completes a warp jump, Doctor Sakezo Sado completes a physical examination on Captain Okita. While warping has had no apparent ill effects on his health, the good doctor nonetheless cautions Okita to be mindful of his well being. Niimi approaches Okita with plans to scout out a nearby planet that would be suitable for colonization in the worst case scenario, but the Yamato shudders as a solar flare from a nearby sun temporarily immobilizes it.
Okita proposes moving through a weak point in the solar flare to proceed, but the Yamato is attacked from behind by Schulz. The torpedo Schulz launches is intercepted by AA fire, but the explosion unleashes an artificial gaseous lifeform that feeds on energy. This is the prototype weapon Desslar gave to Schulz: the Desslar Torpedo.
With the gaseous lifeform threatening to obliterate it, the Yamato is left with no choice but to fly towards the star, placing it between a rock and a hard place. Okita suddenly collapses in pain. Sado and Harada tell the crew it's merely fatigue from overwork. Eventually, the Yamato flies close enough to the star that the gaseous lifeform goes after it instead and is absorbed into the star.
With little else to lose, Schulz orders his crew to pursue the Yamato as it flies over the surface of the star. As a massive solar prominence threatens to engulf the Yamato, Okita recovers and orders Kodai to fire the Wave Motion Gun at the prominence. The Wave Motion Gun creates a hole in the prominence, allowing the Yamato to fly through while Schulz's ship is consumed by it, destroying it and killing all on board.
Gremto Goer, Schulz's superior officer, attempts to place all the blame for the operation's failure on Schulz and his men. Desslar cuts him off and orders Schulz and his men promoted two ranks posthumously, as well as the families of all the ship's crew promoted to honorary citizens in honor of their service. As Desslar departs, talk spreads of the Wave Motion Gun being very similar in design to a prototype currently being developed by Garmillas...
Whenever Alter was alone, it was stealthily search through the Yamato's databases. During a few such excursions, it encounters a "goddess", and it becomes determined to pursue her at all costs. Alter escapes its confines in search of the "goddess", sending the ship into a panic.
Analyzer, realizing that there is only one recourse in order to protect the Yamato, finds Alter on the outer hull of the ship. It hacks into Alter's database and destroys it from the inside, in essence killing the only synthetic friend it ever met.
The Yamato encounters a Garmillan ship that is also trapped in the rift. Since both ships need the other's help in order to escape, they set aside their differences for the time being. The Garmillans send one of their fighter pilots to the Yamato as a show of goodwill: Lower Storm Leader Melda Dietz, the daughter of Garmillas's cosmic fleet admiral Gul Dietz.
A plan is formed between the two ships: the Yamato would use its Wave Motion Gun to open a hole in the rift through which to escape. Since this would consume most of the Yamato's remaining energy and thus leave it stranded, the Garmillan ship would tow the Yamato safely out of the rift.
After creating the opening in the rift, the plan is almost sabotaged by a Garmillan official that severs the tow cables. The official is shot and killed by one of the crew, and both the Yamato and the Garmillan ship escape.
Unfortunately, waiting for them outside the rift is a fleet of ships lead by Goer, who orders the Garmillan vessel shot down (without regards as to whether Melda Dietz was still aboard), then to sink the Yamato. The Yamato manages to escape as many of Goer's vessels are trapped in the rift, but Melda now finds herself stranded on the Yamato.
While being interrogated by Kodai, Melda claims that the Earth fleet attacked the Garmillans first, and thus provoked the war between them. Shima does not believe her: his father was the captain of a ship that was part of the fleet that made first contact, and was also among the ship's casualties. As Captain Okita would reveal to Kodai, as well as Chief Engineer Yamazaki to Shima, Melda spoke the truth:
Okita was the leader of the fleet that made first contact. General Serizawa ordered Okita to launch a preemptive attack on the Garmillans, but Okita refused. As punishment, Serizawa stripped Okita of his command. The Earth fleet attacked the Garmillans and was nearly wiped out. Yamazaki was the sole survivor of the ship Shima's father captained, and corroborates Okita's story.
Shima is still in denial, refusing to believe Yamazaki.
As for Melda Dietz: she forms a rivalry with one of the Yamato's pilots, Yamamoto. The two engage in a dogfight so that Yamamoto could carry out revenge for the death of her brother. Her fighter malfunctions, though, and she is forced to eject. Thankfully, Dietz rescues her and returns her to the Yamato. Yamamoto is given six days in the brig for her actions, but she doesn't mind: the hatred she had harbored for the Garmillans had dissipated.
Kodai gives Dietz food and supplies for four days before she leaves to return to Garmillas, the two harboring mutual feelings of respect towards one another. Dietz leaves the Yamato on friendly terms.
Back on Garmillas, Desslar asks Domel to oversee the Milky Way Theatre, and to sink the Yamato. Being a loyal soldier, Domel abides Desslar's request.
Meanwhile, on the Yamato, tempers flare between Kodai and Shima over their opposing views on the Garmillans. Okita orders them both to clean the ship, top to bottom, to cool off their tempers. Shima tries to come to grips with his anger over the Garmillans, with some help from Yamamoto after she is released from the brig. Eventually, he and Kodai make amends and proceed with the mission.
However, the Yamato soon comes under attack by an unseen enemy...
To this end, as the Yamato releases a sonar ping, Kodai commandeers a recon ship and releases sensor buoys. Thanks to Kodai's quick thinking, the Yamato is able to anticipate the UX-01's attacks and disable its periscope, allowing it to escape.
Meanwhile, at Garmillas, Domel lays out his plan for an ambush on the Yamato. At the same time, a massive fleet of Garmillan ships is gathering at the Garmillan forward base at Balun. Desslar approaches a subspace gate to visit Balun, but his ship is suddenly engulfed in an explosion, killing him and all aboard.
Later, two Gamillan dreadnaughts appear behind the Yamato, forcing it to warp ahead. This turns out to be a trap, as waiting form them just beyond their warp point is a fleet of Garmillan battleships led by Domel. Okita commands the ship to charge straight through the ambush. The Yamato takes heavy damage and is mere moments away from being sunk. Before the finishing blows can be delivered, Domel is suddenly recalled to the homeworld.
Meanwhile, back on the Yamato, Niimi proposes abandoning the Yamato's mission in favor of resuming Project Izumo: before the Iscandarians sent Earth the plans for the Wave Motion Engine and its Core, Project Izumo was proposed to find a planet suitable for human colonization in the event of Earth becoming inhospitable. XO Sanada refuses to abandon the mission. At that point, Itou and his security team begin a mutiny, taking over the ship and placing Shima in charge as acting captain by claiming that Okita was unable to fulfill his duties due to his illness. They make ready to return to Earth...
The away team manages to find a Wave Motion Core inside an old building that was built by a long lost civilization. As they return, the Yamato prepares to leave the planet. At the last minute, however, Shima opens a bay door to let the away team back aboard. Itou demands he abandon Kodai and the away team, but Shima refuses. Itou prepares to kill Shima, but is stopped by Niimi, who has a pang of conscience during the mutiny. Itou prepares to shoot her, but is stopped by Toru Hoshina, a security officer who worked for Sanada as a counter-mole within the Project Izumo rebels and convinced Shima to help him.
As for the Yamato, it arrives at the subspace gate that was revealed in the Wave Motion Core Kodai found on Beemela-4. If activated, it could act as a shortcut for the Yamato, making up for much of the time she lost. An away team consisting of Kodai, Mori, and Sanada enter the gate's control chamber to investigate whether it can be of any use.
During the course of the mission, Sanada reminisces about Mamoru Kodai, who was his best friend and, for a time, Niimi's boyfriend.
Eventually, the away team reaches the core room of the subspace gate. Sanada seals himself in as he activates it, knowing that the resulting neutron radiation burst could kill him, and reveals to Kodai that he knew Operation M was but a diversion, yet he said nothing about it to Mamoru before he left, leaving him with a book of poems from Chuya Nakahara, which he kept with him. Ultimately, though, Sanada survives the subspace gate's activation by diving into a pool of water nearby (since water blocks neutron radiation fairly well). With the gate back online, the Yamato may make time yet.
Finally, Captain Okita makes a startling announcement to everyone on the Yamato: an Iscandarian is among them. It is not Mori, as was initially suspected, but Yurisha Iscandar, the first Iscandarian emissary, who now lay comatose in the Automatic Navigation room, her memories plotting their course to Iscandar. Yurisha has also found a way to communicate with the Yamato crew: by using Yuria Misaki as a medium.
With the subspace gate's viability now confirmed, the Yamato travels through, arriving at Balun. Zoellik, who now leads the fleets at Balun, orders all ships to attack the Yamato. The result is disastrous for the Garmillan fleets, as many are sunk due to collisions and friendly fire.
As the Yamato seems to sink into Balun's core, Desslar suddenly appears on monitors throughout the Garmillan fleet and empire. Desslar reveals that he knew of Zoellik's attempt to usurp him and escaped to safety with Wolf Frakken, and the one Zoellik had assassinated was a body-double. When Zoellik tries to justify his actions, Goer shoots and kills him.
Suddenly, the Yamato re-emerges and fires its Wave Motion Gun at Balun's core, using its recoil to escape through another subspace gate while using the explosion from Balun to wipe out most of the fleets stationed there.
To continue its journey, the Yamato would have to traverse the Rainbow Cluster: seven nebulas that house powerful ionic storms. At the same time, Domel's fleet await them for a final, decisive battle.
Unfortunately, the Zaltzi commandos kidnap Yuki, mistaking her for their Iscandarian quarry, and escape. Shortly afterwards, the Iscandarian reveals herself to Susumu and introduces herself as Yurisha Iscandar.
As the Garmillans prepare to send Yuki to their homeworld, rebel Garmillans start a massive jailbreak. Admiral Dietz is freed by his daughter Melda, and Itou is killed in the fighting. The lone surviving Zaltzi commando from the Battle of the Rainbow Cluster manages to escape with Yuki, however.
The Yamato sets course for Garmillas to rescue Yuki, and make a frightening discovery: Garmillas and Iscandar are twin planets!
The Yamato makes the last warp jump to Garmillas and Iscandar.
Susumu goes to pursue the Desura to rescue Yuki, while Okita uses the Wave Motion Gun to vaporize Second Beleras, saving countless innocent Garmillan lives in the process.
Onboard the Desura, Yuki plans to sabotage the Desslar Cannon, saving the Yamato while sacrificing herself. The Zaltzi soldier, however, tosses her out the airlock, saving her while he sacrificed himself to sabotage the cannon and destroy the ship.
Susumu and Yuki are finally reunited in space as Iscandar comes into view.
As Starsha deliberates as to whether to give the Yamato the Cosmo Reverser, she learns from Garmillas of Desslar's demise, and the part the Yamato played in saving innocent Garmillans from death.. Her younger sister, Yurisha, also speaks up for the Yamato. Finally, Starsha decides to give the crew of the Yamato the Cosmo Reverser. She reveals that the Iscandarians had learned to weaponize Wave Motion energy long ago, and that it lead to her people's near-extinction. She also reveals that the Cosmo Reverser requires the memories of someone who lived on Earth before the war with Garmillas in order to function. The core of the system is actually the memories, the very soul, Susumu's older brother, Mamoru Kodai: he survived his last stand with the Garmillan fleet during Operation M, but was taken prisoner. The ship he was trapped on crashed on Iscandar. He was the sole survivor, but his injuries were grave and Starsha couldn't stop him from dying. She helped him record a final message for Susumu, however, and transcribed his memories into the Cosmo Reverser.
With the Cosmo Reverser, the Yamato departs, and Starsha gives her final farewells to the ship's crew, and to Mamoru...
Not all is well, however: Yuki is grievously injured in the fighting...
Back in his private quarters, Okita watches as Earth finally comes into view. He quietly passes away, and the Cosmo Reverer miraculously reactivates shortly thereafter.
Thus, on December 8, 2199, the Yamato completes its mission and saves the Earth.