Green Day is performing at Lake Springfield, where they start talking about the environment and all the fans get irritated. Greenday were killed when the pollution in the lake as it eats away their vessel, causing it to sink. At the funeral, Grampa Simpsons has a vision of a bad fate for Springfield, but only Marge listens. Lisa and an Irish boy named Colin hold a seminar called "An Irritating Truth", which convinces the town to clean up the lake. Homer dares Bart to skateboard nude to Krusty Burger, but Bart is caught by Chief Wiggum. Ned Flanders is nice to Bart after he was humiliated but Homer doesn't care and adopts a pig. Homer kept the pig's waste in a silo, which Marge tells Homer to get rid of. When Homer waiting in line at the dump, Lenny, Homer's friend calls him to tell him that they are giving away free donuts so Homer decides to do the quicker thing and dumps the silo into the lake, which makes the pollution to be at an all-time high. Flanders and Bart go on a hiking trip and discover a mutated squirrel, which is captured by the EPA. Russ Cargill, head of the EPA, tells President Schwarzenegger that Springfield is very polluted and the government must take extreme action, so the EPA places Springfield in a giant glass dome. An angry mob burns down the Simpsons' house, and tries to kill Homer, but when Maggie discovers a hole from their sandpit to the outside, they run off. Homer wins a car to get around faster from a motorbiking dome. However, the EPA is looking for them so they escape to Alaska. When they get word that Springfield is going to be bombed and destoryed, Marge and the kids go back, leaving Homer behind because he doesn't want to go back to be killed. Eventurly, he does go back with the persuasion of an Indian only to realize that the EPA has caught his family and put them back in Springfield. Homer goes back inside the dome too, and with his motorbiking skills to ride up the top of the dome with the bomb and threw it outside, smashing the glass dome into pieces and freeing the Springfield residents.
The movie featured the band Greenday at the start, and in one scene features over 320 characters. Before its release, the movie received a nomination in the category "Best Summer Movie You Haven't Seen Yet" at the 2007 MTV Movie Awards, but it lost to Transformers. The movie's trailer won a Golden Trailer Award in the category "Best Animated/Family Film Trailer" at the 8th Annual Golden Trailer Awards.
The movie took 6 years to make, as the creators had many ideas and couldn't decide what to do at first. "Two film's worth" of material was cut in the end.