It is the year 2100, and on the colonized Moon, a project is under way to explore new aspects of energy. Amami Kurau is the daughter of the chief scientist on the project, and on her 12th birthday, she accompanies her father to the lab to observe the experiments. Then something goes awry, and Kurau is struck by twin bolts of light. In the aftermath, her father is dismayed to find that his daughter is no longer his daughter. Rather, her body is now home to two energy entities with fantastic powers.

Three years since the return of the legendary Space Battleship Yamato, Earth has begun rebuilding itself and has made peace with the Gamilans. However, this recovery comes at the cost of utilizing the forbidden Wave Motion technology. Meanwhile, the notorious former crew members of the Yamato, who have each gone their separate ways, receive a psychic message from the mysterious Goddess Teresa. She urges them to return to their beloved ship and travel to the distant planet Terezart. They are promised a revolutionary power to combat the unprecedented threat of the relentless Gatlantis Empire, who are approaching Earth with all but innocent intentions. Unable to resist her plea, the crew reassembles and sets sail on another perilous intergalactic voyage, one that will test their sheer courage and versatility in the face of an even greater foe.

In the year 2201, one year after the Yamato saved Earth from radioactive contamination, a new threat emerges. The Yamato makes its final journey to save the Earth from this new threat. Earth has almost recovered from the battle against Gamilus, and reconstruction has expanded to the other planets. When former Yamato crew-mates discover a strange, garbled message that seems to be coming from a white comet headed towards Earth, they hijack their old space fortress and begin a new battle.

2199 AD. Yamato tried to leave behind the Large Magellanic Cloud galaxy, after receiving a "Cosmo Reverse System" at its destination, Iscandar. However, suddenly, it encounters a mysterious group at the edge of the Large Magellanic Cloud. The crew finds out that the group is called the "Gatlantis," and that its leader is the Gutaba expeditionary force commander who calls himself "Goran Dagaamu of Thunder." The commander demands that Yamato be handed over to him. Yamato, wanting to hurry to Earth, escapes the fray. However, Yamato is attacked by a devastating beam weapon called the "Flame Direct Attack Cannon" that can transcend space. Yamato was able to retreat, but ends up getting lost, and finds itself in a strangely colored irregular dimension. The crew decides to turn off the engine on the ship, and explore a mysterious planet. In order to collect information, Kodai, Kiryū, Sawamura, Niimi, and Aihara land on the planet. What they saw when they arrived was a ship that was not supposed to be there. Dagaamu chases after the traces of Yamato's warp, and also reaches the strangely colored space. The planet on which Yamato landed was in fact what Dagaamu had been looking for all along.