In Oddworld: Abe's Oddysee Abe shut down RuptureFarms and saved his buddies from becoming snacks. But Rupture farms was just the beginning; the Glukkons are digging up bones at the ancient Mudokon burial grounds. They use the bones to make Soul Storm Brew. Abe must travel to the Soul Storm Brewery, stop those corporate villains and save the enslaved Mudokon workers.

Oddworld: Abe's Exoddus is a 2D platform game very similar to its predecessor both visually and gameplay-wise. Like in the previous game, Abe has to outsmart his foes and avoid obstacles rather than confront them directly. The game is larger than its predecessor and is more oriented towards puzzle-solving, featuring more complex interaction with the Mudokons, who can now be angry, wired, depressed, sick, or blind. The first three problematic conditions can be removed with the appropriate "Gamespeak" command; sick Mudokons must be cured with a special item, while blind ones will follow Abe's voice and may fall to their deaths if Abe doesn't stop them in time.

An additional ability Abe has is turning into a Mudokon deity called Shrykull, which possesses the power to instantly kill enemies. Transformation into Shrykull is possible only if Abe succeeds in sending several Mudokons through the bird portal at the same time. After having used Shrykull's power once, Abe transforms back into his normal Mudokon self.

As opposed to the predecessor with its limited saving possibilities, a quick save feature has been added to Abe's Exoddus. The player can save at any time and resume playing from the same spot in case Abe dies.