Representing his co-stars, Robert De Niro, Jennifer Lawrence, Amy Adams and Christian Bale, actor Bradley Cooper praised film director David O. Russell.
As actors form the biggest voting bloc in the Oscars, the SAG awards are seen as a key indicator for that ceremony.
Last year, the guild chose hostage drama Argo for its top honor, with that film going on to receive the Academy Award for best picture.
However, this year’s field is more competitive – with 12 Years a Slave and Gravity expected to give American Hustle‘s A-list cast a run for their money when the Oscars roll around on 2 March.
Newcomer Lupita Nyong’o, who plays an abused plantation worker in 12 Years a Slave, was given the best supporting actress award by SAG voters.
The Kenyan actress also thanked her director, British film-maker Steve McQueen, “for taking a flashlight and shining it underneath the floorboards of this nation and reminding us what it is we stand on”.
Both best actor and best supporting actor went to the stars of Dallas Buyers Club, a small film that cost just $4 million to make.
The film is based on the true story of a homophobic Texan who gets AIDS and smuggles unapproved anti-HIV drugs into the US in the 1980s.
Matthew McConaughey, in the lead role, and Jared Leto both endured dramatic weight loss to play their parts.
Cate Blanchett took home the best actress prize for her complex, cracked portrayal of a socialite fallen on hard times in Woody Allen’s Blue Jasmine.
It was Cate Blanchett’s 17th best actress prize of the awards season – and she is considered a near-certainty for the trophy at both the BAFTAs and Oscars.
The SAG Awards also recognize actors working in TV, with sitcom Modern Family winning best ensemble in a comedy series and best male actor in a comedy series for Ty Burrell’s dumb-but-loveable patriarch Phil Dunphy.
Accepting the show’s cast award – its fourth in a row – Colombian star Sofia Vergara said the honor was “mind-blowing”, adding: “I can barely speak English.”
Breaking Bad, which left TV screens last year, continued its victory lap around the awards shows, winning outstanding dramatic cast and for best lead actor Bryan Cranston, for his indelible performance as teacher-turned-meth dealer, Walter White.
Maggie Smith and Helen Mirren won best actress awards for Downton Abbey and the TV movie Phil Spector respectively.
Michael Douglas picked up a best actor prize in the TV category for his performance as Liberace in the movie Behind The Candelabra, which was only shown on cable channel HBO.
The lifetime achievement award was given to Rita Moreno, the 81-year-old actress who played Anita del Carmen in West Side Story, alongside roles in Singin’ in the Rain and The King and I, and on Broadway in The Ritz and The Odd Couple.
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