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From the White House in Washington DC, First Lady Michelle Obama joined actor Jack Nicholson here at Dolby Theatre to help present the final prize.
The film was the bookies' favourite going into the event, having already been named best film at the BAFTAs and best drama at the Golden Globes.
Affleck sped through his acceptance speech, and his voice cracked while he thanked his wife Jennifer Garner.
"Thank You. Steven Spielberg is a genius, a talent among us. I want to acknowledge the other great films that have as much right to be up here as we do and many of them who did not even get nominated this year.
"I want to thank my brother, mom, dad. I want to thank my friends in Iran. I thank my wife. I am here because of so many of people, who have taught me to work harder than you possibly can. It does not matter how you get knocked down in life," Affleck said.
Played out against the backdrop of the 1979 hostage crisis, 'Argo' spins the account of a joint Hollywood-CIA mission to spring six imperiled Americans from revolutionary Iran, using a fake movie production as a decoy.
The film stars director Affleck as a CIA agent, while the supporting cast includes John Goodman, Bryan Cranston and Alan Arkin. 'Argo' is Affleck's third stint in the director's chair – after 'Gone Baby Gone' and the Boston crime drama 'The Town' and by far his most successful.
