Plot

Itchy and Scratchy land on the Moon as part of the Apollo mission. Itchy says that they come in peace for cats and mouse everywhere. Scratchy responds by stabbing Itchy with the flagpole and breaking his helmet, thereby killing him. Scratchy takes off in the Apollo module and returns home a hero. Scratchy is credited with trying everything to save Itchy. After a parade, Scratchy is eventually elected President of the USA. Scratchy looks at the moon through his binoculars and finds that Itchy is alive. Scratchy launches all the nuclear missiles at the moon, blowing Itchy to smithereens. Turns out this was a movie, and Homer finds it boring and calls everybody in the audience a sucker for paying to see something that they get on TV for free.

After finishing a concert at Lake Springfield, Green Day tries to engage the audience in a discussion about the environment, but they refuse to listen and throw garbage at them. The pollution in the lake erodes the band's barge, causing them to be drowned and leading to their death.

During their memorial at the town church, Grampa Simpson has a spiritual experience and frantically prophesies that a disaster will befall Springfield, which only Marge takes seriously. Grampa talks about twisted tail, a thousand eyes, trapped forever and that time is short. Grampa screams EPA, EPA before passing out.

Homer returns home and ignores the sinkhole that is developing in his backyard but covering it with Maggie's sandbox. Home and Bart go to re-shingle the roof, but then engage in a dare contest leading to Bart hanging off the roof. Ned tries to counsel Homer that Bart could be severely injured, but they both ask Ned to mind his own business.

Concerned about the terrible state of the environment, Lisa and her new friend Colin hold a seminar and convince the town to clean up the lake. Colin is a new kid at school who has moved from Ireland and his dad is a musician.

Meanwhile, Homer and Bart continue to engage in the dare contest, in which Homer dares Bart to skate across town naked to the Krusty Burger place. After being caught by the police, Homer allows Bart to take the blame for the dare. Homer brings a shirt for Bart, but no pants. As Bart enters a Krusty Burger joint, he finds Ned who says that he is carrying an extra pair. Ned helps Bart and says that Homer would do the same for his boys.

At Krusty Burger, Homer adopts a pig (Krusty ordered the pig to be killed after the advertisement was shot) to save it from being slaughtered. Marge, identifying the pig as a part of the prophecy (a twisted tail), warns Homer to get rid of it, but he refuses and names it Spider-Pig, then renames him Harry Plopper. Homer's fawning over Plopper makes Bart, now fed up with Homer's carelessness, to look to their neighbor, Ned Flanders, as a father figure. Ned makes a delicious cup of cocoa for Bart and promises to take him on a fishing trip. Bart remembers that Homer used a bug zapper to catch fish when they went fishing. When Bart makes a mistake, Ned does not strangle him and gently pats him on the back.

At a town hall meeting, Lisa makes an impassioned plea that the lake is just one piece of trash away from total disaster. The mayor agrees and bans any more dumping in the lake. The town comes together to stop all sources of pollution going into the lake. The mayor also installs a concrete barrier all around the lake, so contaminants cannot be dumped via land.

Marge orders Homer to dispose of an overflowing silo full of Plopper's feces. Homer takes the silo to the hazardous waste disposal center, but then gets a call that the Lard Lad Donut shop is being shut down by the health inspector and they are giving away their inventory for free.

Rather than waiting in line to dispose the silo safely at Marge's request, Homer dumps the silo in the lake, critically polluting it, in order to arrive at the closing Lard Lad Donuts in time to get free donuts. When a squirrel jumps into the lake, it comes out horribly mutated, with a thousand eyes.

The EPA arrives and takes the mutated squirrel away. Russ Cargill, head of the Environmental Protection Agency (EPA), informs President Arnold Schwarzenegger of Springfield's pollution crisis and presents him with five solutions. Schwarzenegger then randomly picks the third option - sealing Springfield off from the rest of the world under a giant glass dome. Marge laments that all predictions have come true, including the town being trapped forever under the dome. The Homer home is at the very edge of the dome. Meanwhile, Maggie discovers a sinkhole that leads to outside the dome, in her sandbox.

Being trapped under the dome causes mass hysteria in Springfield and when Homer's silo is discovered on the news, hundreds of townspeople arrive at the Simpsons' house in an attempt to lynch the family. They escape through a sinkhole hidden under Maggie's sandbox (Maggie points to the sinkhole and jumps through it to demonstrate to the family that it is an escape route). The mob destroys the house by setting it on fire (the only things that Marge saves is her wedding video tape) and then the sinkhole swallows the house, sealing it forever.

The family is furious at Homer for his blundering, but he convinces them to follow him to Alaska, where he had always planned to go if something like the incident happened. Homer wins a pickup truck by riding a motorcycle around a globe of death (Lisa tells Homer not to slow down when he is at the top and to instead speed up) and the family restarts their lives in a remote Alaskan cabin. Upon arrival they are paid $1000.

Meanwhile, day 37 under the dome, and Springfield exhausts its supplies, the townspeople attempt to find another way to escape from the dome. The town starts having intermittent power failures and is forced to buy electricity from Monty Burns. Moe's bar is stripped clean when the light goes out.

By Day 93 under the dome, the residents are desperate and try to destroy the dome. Cargill, mad with power, tricks Schwarzenegger into ordering the town's demolition. The Simpsons see Tom Hanks on television advertising a "new Grand Canyon" on the site of Springfield. Realizing that their hometown is in danger, the family vow to save it, except for Homer, who refuses to partake because of how their friends had turned against them and storms out. When he returns the next morning, he finds his family gone and a videotaped message from Marge explaining that she and their children are returning to Springfield to save it. To prove that her decision is permanent, she tapes her message over their wedding video.

An Inuit shaman then helps a distraught Homer to have an epiphany about his selfishness and he vows to save the town. Meanwhile, Marge and the kids are captured by the EPA in Seattle and placed back inside the dome. The town is nearly destroyed, but to Bart's disappointment, the school is untouched.

Homer takes a dog sleigh to travel through to Alaska, but the dogs attack Homer after a day of non-stop whipping. The Shaman lady again arrives in a vision and points Homer in the direction of Springfield.

The EPA lowers a time bomb suspended by a rope through a hole at the top of the dome, and the townspeople try to escape by climbing the rope. Homer returns to Springfield and descends the rope, knocking the escaping townspeople and the bomb off, inadvertently shortening its countdown and further provoking the town's ire.

Homer reconciles with Bart, and they use a motorcycle to travel up the side of the dome with the bomb. Bart throws the bomb through the hole seconds before it detonates, shattering the dome and freeing the town. Cargill attempts to murder Homer and Bart for foiling his plan, but Maggie knocks him out by dropping a rock on his head. The townspeople forgive and praise Homer before he rides into the sunset with Marge as Springfield begins restoration. Lisa reconnects with Colin.