A U.S. Army librarian, Corporal Joe Bauers (Luke Wilson), and a prostitute, Rita (Maya Rudolph), are selected for a suspended animation experiment on grounds of ‘average’ appearance, intelligence, behavior, etc. Rita’s pimp “Upgrayedd” (Brad Jordan) has been bribed to allow her to take part. The experiment is forgotten when the officer in charge (Michael McCafferty) is arrested for having started his own prostitution ring under Upgrayedd’s tutelage. Five hundred years later, Joe and Rita’s suspension chambers are unearthed by the collapse of a mountain-sized garbage pile, and Joe’s suspension chamber breaks through the wall of Frito Pendejo’s (Dax Shepard) apartment, whose occupant expels him.
Joe, suspecting hallucination, enters a hospital. The former Washington, D.C. has lost most of its infrastructure, with people living in plastic huts called “domistile”. The human population has become morbidly stupid, speak only low registers of English competently, and are profoundly anti-intellectual. When Joe is arrested for not having a bar code tattoo to pay for his doctor’s appointment, he realizes the current year and society’s state. At Joe’s trial, Frito, acting as his (grossly incompetent) lawyer, causes him to be sent to prison. Rita returns to her former profession.
Joe is renamed “Not Sure” by a faulty tattooing machine, and takes an I.Q. test before escaping. Once free Joe asks Frito whether a time machine exists to return himself to 2005, and Frito agrees to find one after Joe promises to open a bank account under Frito’s name in Joe’s time, which will be worth billions by 2505. On the way, Joe reunites with Rita, and the three arrive at a gigantic Costco store, where a tattoo scanner identifies Joe as a fugitive. He is taken to the White House, where he is appointed Secretary of the Interior, on the grounds that his I.Q. test identified him as the most intelligent man alive. In a speech, President Camacho (Terry Crews) gives Joe the job of fixing the nation’s food shortages, dust bowls, and crippled economy within a week; whereafter Joe discovers that the nation’s crops are irrigated with a sports drink named “Brawndo”, whose eponymous parent corporation had purchased the FDA, FCC, and USDA. When Joe has it replaced with water, Brawndo’s stock drops to zero, and half the population lose their jobs, causing mass riots. Therefore Joe is sentenced to die in a monster truck demolition derby featuring undefeated “Rehabilitation Officer” Beef Supreme (Andrew Wilson), when Rita discovers that Joe’s reintroduction of water to the soil has prompted vegetation in the fields. Frito shows the crops on the stadium’s display screen, and Camacho gives Joe a full pardon, appointing him Vice President. Joe and Rita find that the time machine Frito named is an inaccurate, history-themed amusement ride. Following Camacho’s term, Joe is elected President. Joe and Rita marry and conceive the world’s three smartest children, while Frito, now Vice President, takes eight wives and fathers 32 of the world’s stupidest children. A post-credits scene shows a third suspension chamber releasing Upgrayedd, intent on tracking Rita down.