After defeating Mr. Dark in the previous game, Rayman, our hero is enjoying a calm relaxing life. But, as game stories go, things rarely stay quiet for long. When an armada of Robo-Pirates invades the universe, destroying planets by the numbers and enslaving their inhabitants things turn sour. Upon reaching the Glade of Dreams, they meet resistance from Rayman and his allies. They get captured and thrown onboard the Buccaneer, a prison ship. Thanks to Globox, Rayman is able to escape, however with all his powers missing. First order of business is to find Ly the fairy in order to restore them.

Upon meeting with her, Rayman learns that in order to free Rayman's friends, he must defeat barbaric pirates and gather the 4 masks of Polokus. Rayman 2: The Great Escape marks the series' first foray into the world of 3D, which means new gameplay mechanics and challenges to overcome. In total, there are over 40 levels, including four bosses to overcome. Levels usually requires a mix of both fast platforming and puzzle solving in order progress. Finding all lums and imprisoned friends on a level unlocks a bonus stage.

The game was ported to a wide selection of platforms, including the Game Boy Color, Sega Dreamcast and both PlayStation (1 and 2) platforms at the time. Originally, Rayman 2 was developed as a 2D sidescrolling platform game, similar to the first. However, when development shifted to 3D the prototype was scrapped. This level is actually unlockable in the Sony PlayStation version, if the player collects a total of 720 yellow lums (out of 800, which was that platform's max).