Uchū Senkan Yamato: Nijū Ginga no Hōkai is the third and final part of the "Dark Nebula series", after Uchū Senkan Yamato: Iscandar e no Tsuioku and Uchū Senkan Yamato: Ankoku Seidan Teikoku no Gyakushū. It follows the events of the second half of the fourth Yamato movie, Be Forever Yamato. The Yamato and the Yukikaze have finally reached the Dark Nebula, and discover it is actually two parallel galaxies, one of light, and one of darkness. Entering this new universe, the heroes of Earth are about to discover the secrets of the Empire, and engage in a deadly battle to ensure the future of the human race.

Uchuu Senkan Yamato: Nijuu Ginga no Houkai is a very similar to the previous two Playstation 2 games, and feature both the real-time space battles and third-person phases, where the player takes direct control of a character and must navigate 3D levels to accomplish specific objectives. Like previous games of the series, the game features character-design by Keisuke Masunaga, based on the original characters created by Leiji Matsumoto. The story is told both with animated 2D movies and fully-voiced in-games cutscenes. The characters are rendered in cel-shading. The game's story is based on co-creator Leiji Matsumoto's original ideas and is quite different from the movie, offering two possible endings.