The games begins with Rayman and Globox sleeping in the Fairy Council, when Globox's dreams are disturbed by the memory of him swallowing the Black Lum Andre. He is awakened by a strange sound, and goes off to search for its source (it is possible he was captured by the Hoodlums, since he is later seen in the Bog of Murk, seemingly trapped). Later, Rayman wakes up to find his pal missing, and goes off to look for Globox.
As he journeys onward, Rayman is told by Murphy that the Hoodlums are trying to clone Reflux, the other main rival of Rayman 3, and that the clone is plum juice-powered. Before he finally meets up with Globox, he must destroy the Infernal Machine, which basically makes the potent plum juice.
Meanwhile, in the Bog of Murk, Globox is unknowingly being slowly taken over by Andre, and this is apparent by Globox's sudden mood swings in which he become condensending, aggressive, and just plain mean. Later, when he and Rayman are reunited, he often insults Rayman or the feeble attempts of the Hoodlums ("meddlesome loser" and "Lame-man" are some of the jeers he threw at Rayman). However Rayman, unused to Globox being a jerk, or smart in any way, simply did not hear most of it, though at one point he asks Globox if he was hit in the head.
As they continue through the lands they must save The Teensies and defeat a couple of bosses (Begoniax Bayou and Pit of Endless Fire are the boss levels [excluding Infernal Machine and Reflux's Lair]). In the Pit of Endless Fire, after the defeat of the Firemonster, Andre takes full control of Globox and announces his return.
When Rayman finally encounters the cloned Reflux and defeats him, Globox appears as Andre's black spirit flutters away through Globox's mouth, and he awakes his full self, even asking if he missed breakfast. The story ends with the pair walking off into the forest.