A global cataclysm occurs which leads to the end of the world and has survivors struggling for their lives, while a US government agency called the "Institute for Human Continuity" attempts to use ships to ensure the survival of the human race.
The film is inspired by several hypotheses that state that the ancient Mayan predicted a doomsday event would occur sometime around the 2012 northern hemisphere winter solstice.
Disaster movie maven Roland Emmerich (Independence Day, The Day After Tomorrow) crafts this apocalyptic sci-fi thriller following an academic researcher who opens a portal into a parallel universe, making contact with his double in an effort to prevent the catastrophic prophecies of the ancient Mayan calendar from coming to pass. According to the Mayan calendar, the world will come to an end on December 21, 2012. When a global cataclysm thrusts the world into chaos, divorced writer and father Jackson Curtis (John Cusack) uses his knowledge of the ancient prophecies to ensure that the human race is not completely wiped out. Chiwetel Ejiofor, Danny Glover, Amanda Peet, Thandie Newton, and Oliver Platt round out the cast of this end-of-the-world thriller co-scripted by the director and his 10,000 B.C.
- John Cusack as Jackson Curtis, a science fiction book writer who occasionally works as a limousine driver.
- Chiwetel Ejiofor as Adrian Helmsley, scientific advisor to the President.
- Amanda Peet as Kate, Jackson's ex-wife.
- Thandie Newton as Laura Wilson, the First Daughter.
- Oliver Platt as Carl Anheuser, the President's Chief of Staff.
- Danny Glover as President Wilson, the President of the United States.
- Woody Harrelson as Charlie Frost, a man who prophesies the end of the world and is considered crazy by others. Alex Jones claimed in an interview with Eric "Mancow" Muller that Harrelson told him that Frost's character was based on him. Harrelson compared his character to the mythological Greek figure Cassandra, whose predictions were dismissed.
- Ng Chin Han as Lin Pang, a worker in Tibet.
- Thomas McCarthy as Gordon, Kate's current boyfriend and a plastic surgeon.
- Liam James as Noah Curtis, Jackson and Kate's son.
- Morgan Lily as Lilly Curtis, Jackson and Kate's daughter.