The win solidifies "Argo" as an Oscar front runner, after the film also claimed key honours from the Screen Actors and Producers guilds last weekend, reported Los Angeles Times.
"I don't this makes me a real director, but I think it means I'm on my way," Affleck said in a speech at the ceremony which was held at the Ray Dolby Ballroom at Hollywood & Highland.
The other nominees for the feature directing award were Kathryn Bigelow for "Zero Dark Thirty," Tom Hooper for "Les Miserables," Ang Lee for "Life of Pi" and Steven Spielberg for "Lincoln."
The DGA award for feature directing has traditionally been a reliable indicator of who will win the directing Oscar -- only six times since the DGA Awards began in 1948 have the two honours differed.
But this year's Oscar directing race has been a bit of a head-scratcher, Affleck was not nominated, despite his film receiving multiple nominations from the Academy in other categories. Bigelow and Hooper were also snubbed.
The DGA is a larger body than the Academy's directing branch, representing 15,000 members, many of them in television.
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The ceremony's television winners included Rian Johnson, who earned the drama series award for directing the "Fifty-One" episode of "Breaking Bad"; Lena Dunham, who collected the comedy series award for directing the pilot of "Girls"; and Jay Roach, who took the movies for television/miniseries prize for "Game Change" on HBO.
The winner for documentary directing was Malik Bendjelloul, for the "Searching For Sugarman."
A lifetime achievement award was presented to "One Flew Over the Cuckoo's Nest" and "The People vs Larry Flynt" director Milos Forman.