Bart Simpson goes to a video game store and buys a new ultra-violent Grand Theft Scratchy game, which is promptly confiscated by his mother Marge. Suddenly, a video game manual lands right in front of him. Miraculously, after having read the manual, the members of the Simpsons family discover that each of them possesses a unique superpower. Toying with these, however, attracts the attention of the aliens Kang and Kodos, who decide to invade the Earth. Now the unlikely superheroes must not only protect the town of Springfield from an alien assault, but also find the true reason behind their newly acquired powers, and perhaps their very existence.
The PS3 and Xbox 360 versions also contain free-roaming gameplay - exclusively in those versions player characters can leave the Simpsons' house between missions and freely wander through virtual Springfield. Familiar landmarks (such as Moe's Tavern, etc.) are present and can be explored as well. These locations may contain additional dialogue and events. It is possible to use the bus to travel quickly to various destinations.