The movie begins with Homer Simpson purchasing a pig that he intends to raise for a barbecue. However, he neglects to properly dispose of the pig's waste, causing it to contaminate the town's lake. This results in a severe pollution crisis, and the Environmental Protection Agency (EPA) decides to quarantine Springfield by enclosing it in a giant dome.
As the town becomes isolated, tensions rise among its residents, and the situation worsens when the Simpsons are labeled fugitives for defying the EPA's orders to evacuate. Meanwhile, Bart Simpson becomes enamored with a girl named Russ Cargill, who turns out to be a high-ranking EPA official tasked with overseeing Springfield's destruction.
In an attempt to save the town, Homer decides to take matters into his own hands by digging a tunnel to escape the dome. This plan proves rocky and results in a series of hilarious misadventures, including a battle with an angry mob and the activation of a time bomb. Ultimately, the Simpsons must come together as a family to save their town and prevent its destruction.