Reggie the Turkey (Owen Wilson) is pardoned by the President of the United States as per the annual White House Thanksgiving tradition. He lives a comfortable life at Camp David enjoying pizza and telenovelas.

Meanwhile, a turkey named Jake (Woody Harrelson) is the president and the only member of Turkeys Liberation Front. He kidnaps Reggie and the two turkeys travel back in time together to the first Thanksgiving with an important goal in mind: to take turkeys off the menu for all time.