The player controls Ben Tennyson and helps him to travel to five regions across the United States, in order to recover all the Omnitrix's DNA samples stolen by Vilgax, who wants to use it to destroy the world. The gameplay consists of solving puzzles and defeating waves of enemies. Ben also has the access to his Omnitrix, which allows him to transform into different alien forms with specific abilities. At the beginning of the game, Ben is only able to access a few of his alien forms for a limited time, but after defeating a boss, Ben can access a new alien form (Four Arms, Heatblast, XLR8, Cannonbolt, and Wildvine) and unlocks the "master control," allowing him to stay in alien-form for an infinite amount of time, or switch between aliens without draining Omnitrix energy. Attack combos can be unlocked by collecting Omnitrix points. Limited power boosts or invincibility can be gathered, as well as bonuses to make the Omnitrix recharge faster. Three Sumo Slammer cards are hidden in each main level, and unlock features such as movie clips.
After each level, "plumber ranks" are rewarded depending on how fast the player beat the level. If the player gets an A rank, they get a "character view," usually of a boss or a villain. In the main boss levels, a quick time event allows players to execute a special attack at certain points.