The game involves Ben traveling to iconic real-world locations in search of the parts to an ancient Galvan artifact called the Potis Altiare to save the Earth from total destruction by an evil To'kustar. Players control Ben and up to 16 alien heroes including Ultimate Big Chill, Ultimate Spidermonkey, Ultimate Echo Echo, Ultimate Swampfire, Ultimate Humungousaur, Four Arms (PS3) and Rath (Xbox 360).
The game also provides all-new game enhancements such as Quick Switch, which allows players to switch alien forms faster than ever, and Quick Time Events which create a cinematic experience that guides players through fierce boss battles and challenging puzzle elements. Hazard, Armodrillo, AmpFibian, Terraspin and NRG from the Ben 10: Ultimate Alien television series, allowing players to tunnel or beat through alien enemies, unleash water blasts, emit radiation beams, shoot electricity bolts and fire, wind attacks, and more, with a unique experience system which lets them upgrade alien attributes and abilities. Ben 10 Ultimate Alien: Cosmic Destruction introduces the new alien heroes: Water