Continuing the story of the space battleship Yamato after Saraba Uchū Senkan Yamato: Ai no Senshitachi, Uchū Senkan Yamato: Iscandar e no Tsuioku adapts the third movie of the franchise, The New Voyage. When the holy planet Iscandar becomes the target of the evil Dark Nebula Empire, Earth and Gamilas have to put their enmity aside and work together to defend Iscandar. The Yamato takes off for a new galactic odyssey, that will be a baptism of fire for the rookie crew.

Developed by the same team as the two PlayStation games, Uchū Senkan Yamato: Iscandar e no Tsuioku offers a very different gameplay. The semi-turn-based tactical battles are no more, as the game is now a real-time strategy/action game, where the player controls the Yamato and allied ships during 3D space battles. While following the plot of the movie, the game also includes some new twists, characters and adventures on the way to Iscandar.

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.