The local cops are in on the drug ring. They are all arrested by the Highway Patrol, except for Ursula who tipped them off, but their station is shut down anyway. They are all later hired as replacements for the local cops, and they continue to pull their pranks.
In the town of Spurbury, Vermont, the local Highway Patrol (the comedy troupe Broken Lizard) are always pulling pranks on themselves and those they pull over. The Patrol consists of Patrolmen Thorny, Rabbit, Foster, Mac, and Farva. While the first four are on the road constantly having fun, Farva is always manning the radio back at the station. Farva is also the constant butt of everyone's jokes, and when he attempts to prank the others, he always takes it way too far. Their chief, Captain O'Hagen (Brian Cox), who normally doesn't have a problem with the fun they have, tells them that they need to cut back on their shenanigans. Due to budget cuts, their station is on the brink of being closed down, and they need to start doing more serious police work to warrant keeping their station open.
The Patrolmen also have a rivalry with the local Spurbury police, led by Chief Grady (Daniel Von Bargen). This comes to a head when they publicly fight over jurisdiction involving a Winnebago and a dead woman inside it. One day, Foster and Rabbit pull over a semi, which is full of marijuana bricks and all feature a cartoon monkey on the packaging. This same monkey was a tattoo on the dead woman. The Patrol try to investigate the connection between the semi and the Winnebago, but they are blocked by the local cops. Later, Ursula, Spurbury's only female cop, goes to Foster, who is constantly flirting with her, and tells him that she is tired of being mistreated by her coworkers and also thinks they are up to something. She and Foster eventually begin a relationship, which leads to them making out inside the Winnebago. They stumble upon more marijuana bricks with the cartoon monkey on the packaging that the other local cops apparently missed.
Captain O'Hagen and the others decide that the only way to save their station is to steal the Winnebago and present it to the Governor (Lynda Carter), who will be in town later that week. This will show her that they are good at their jobs and she will have no choice but to keep their station open. With Ursula's help, they easily take the Winnebago and drive it to the Governor's reception, but are shocked to find the marijuana that was inside several duffel bags are gone, and the local cops are taking the credit for the bust.
Foster and the rest think Ursula betrayed them, but it was actually Farva. Tired of being mistreated by the others, he was the one who told the local cops about the drugs in the Winnebago, and in return is hired by them to their police force. Believing that their station is now definitely closing, all of the remaining Patrolmen handcuff Farva to a toilet, steal his new police car, and go on a drunken bender. Foster calls Ursula and apologizes to her for thinking she betrayed them, and she tells them to meet her near the airport.
They show up, only to see another semi, similar to the one they pulled over earlier, being loaded with marijuana bricks from a Canadian jet, and the ones loading the truck are the local cops! Ursula then shows up, and she tells them that she suspected this for a while, and she needed the Highway Patrol to shut them down. Just as the Patrolmen are about to enact their hastily made-up plan and arrest everyone, Farva shows up. He thinks the local cops are there to arrest the drug runners, but just as he figures out what is really happening, the Patrol pull up and start a huge brawl. Even though the Patrolmen are still drunk, they easily beat up the local cops and arrest everyone.
The next day, Captain O'Hagen receives a letter of commendation from the Governor, thanking the Highway Patrol for busting a drug ring and police corruption, but she is closing their station anyway. Three months later, Thorny and Mac are now beer distributors, and they arrive with a keg at a frat party. Three frat brothers, who were pranked earlier in the movie, recognize them and try to prank them back. After playing along for a few minutes, the duo have had enough and remove their delivery uniforms and reveal their Spurbury Police uniforms and bust up the party. It turns out that the Mayor of Spurbury fired the entire police force, except for Ursula and Farva, and hired all of the former Patrolmen to become the new local police force. The movie ends with all of the cops, including Ursula and Farva, having fun at the expense of the frat brothers. Farva, as usual, is taking his share of the fun too far.