When Vilgax invades the Earth using a Null Void Projector (which beams Null Void prisoners to Earth), Ben Tennyson with cousin Gwen and friend Kevin Levin, snap into action to defend their hometown Bellwood from the attacks. Splitting up, Ben battles Vilgax’s servant Psyphon, who brings a Mr. Smoothy billboard to life to attack Ben. Ben ends up using most of his Omnitrix aliens to defeat it, but ends up draining the watch’s power as a result. Azmuth, creator of the Omnitrix, appears and tells him that the Omnitrix must recharge before he’ll have access to all of his aliens again, leaving Ben with only Swampfire, Humongosaur, Cannonbolt, Big Chill, and Spidermonkey. Gwen and Kevin show up, along with Professor Paradox, who teleports the gang back to the past to stop Vilgax’s plan before it happens. Paradox gives the trio a message from Grandpa Max, who directs them to the planet Vulpin, home of Wildmutt, one of Ben’s original aliens. Ben calls upon the Galvan Mechamorph Ship to aid them.
On Vulpin, another message from Grandpa Max reveals that Vilgax is using the planet’s refinery to create a piece of alien tech for an unknown purpose. Ben heads off to the refinery alone; along the way, he battles several of Vilgax’s robots, some Vulpimancers, and a giant two-headed snake. When he reaches the refinery, he encounters the Vreedle Brothers and defeats them, and destroys the alien tech, setting fire to the refinery in the process. He reunites with his teammates, who learn of Vilgax’s plan: find an energy core to power his Null Void projector and use it to take over Earth. In another message, Max directs the team to Terradino, Humongosaur’s home planet.
The group arrives at Terradino and learns that the next energy core is located in a nearby temple. Ben gets Goop back and inside the temple, he ends up facing Charmcaster, who wants revenge on Ben for his actions against her uncle Hex. Ultimately, Charmcaster is defeated, Ben destroys the energy core, and the temple begins to crumble. Ben meets back up with Kevin and Gwen and they learn that Max has gone to Encephalonus IV, Brainstorm’s home planet, where an old enemy of Ben’s is waiting for him.
After arriving on Encephalonus IV, Ben gets Brainstorm back, determined to figure out who’s waiting for him. He soon discovers the villain to be Darkstar, who is easily defeated. Ben destroys the next energy core and once again meets up with Gwen and Kevin, and they learn from another of Max’s messages that the final energy core location is Anur Phaetos, home world of Zs’Skayr (a.k.a. Ghostfreak), one of Ben’s former enemies and aliens. However, Vilgax intercepts the message and dares Ben to brave the dangers of Anur Phaetos, if he can even find his way there, since Anur Phaetos is not a planet, but an alternate dimension.
Fortunately, Max sends Ben and Gwen’s Anodite grandmother Verdona to assist the team. Verdona teleports them into Anur Phaetos, but at the cost of getting them separated. Ben ends up facing Zs’Skayr and defeats him, destroying the energy core he was guarding and regaining Echo Echo. Paradox transports the group back to their original dimension, and informs them that Max was lying when he said that Anur Phaetos had the last known energy core in order to throw Vilgax off. He goes on to say that a mysterious being is on Chromastone’s home planet Mor Otesi, using Taydenite to create an energy core that Vilgax can use to take over the Earth.
On Mor Otesi, the gang learns that their old friend Cooper is being tricked into making the new energy core by an unknown villain and Cooper redirects them to the research center where the Taydenite he’s been working on is being kept. Ben regains Chromastone to the Omnitrix and sets off while Gwen and Kevin go with Cooper to sneak in another way. When he reaches the lab, Ben discovers that the mastermind is Albedo, whom he barely manages to defeat. After destroying the Taydenite, Ben meets up with Kevin and Gwen, and Grandpa Max arrives, informing the team that there is one more energy core in existence, but that it’s in the Null Void.
The group then heads there, where Max gives Ben a skeleton key to transport himself into the Null Void, warning him not to destroy the energy core there, but to use it to get back into the main dimension. Ben regains Jetray and heads into the Null Void, where he encounters D’Void/Dr. Animo. Ben defeats him and finds the final energy core, using it to transport back into the main dimension, where no time has passed. Ben also gives Max a picture of them and Gwen from back during the summer where Ben first discovered the Omnitrix.
The group returns home to discover that Vilgax is still invading the Earth, but his Null Void projector is weaker since Ben destroyed all of the known energy cores in existence, save the one from the Null Void. With Max, Gwen, and Kevin holding off Vilgax’s minions, Ben makes his way through Bellwood until he is eventually beamed onto Vilgax’s ship, where he confronts Vilgax himself. After defeating him, Ben has the remaining energy core stolen from him by Psyphon, who attempts to fire raw Null Void energy directly at him at close range. However, Professor Paradox shows up and tells Ben that “now is the right moment”.
Ben then transforms into Alien X (he was going to do it at the start of the game, but Paradox advised him not to, as the time wasn’t right). Alien X then reverses the power of the cannon, sending Vilgax, his ship, and Psyphon through a Null Void portal. Ben changes back to normal, and Azmuth shows up to congratulate him for his work. The game ends with Azmuth adding a new alien to the Omnitrix, to which Ben replies, “Oh yeah! It is seriously hero time, now!”