As expected Daniel Day-Lewis won best drama actor for his portrayal of Abraham Lincoln, but that was the only top award for Spielberg's film, which had topped the nominations tally with seven at the 70th annual Globe awards.
And favorite Jessica Chastain meanwhile won best drama actress as a relentless CIA agent tracking down Osama bin Laden in Kathryn Bigelow's "Zero Dark Thirty," while Quentin Tarantino's "Django Unchained" won two key prizes.
But the night, to the surprise of some, belonged to Affleck, who took the top two prizes.
The actor-director, who plays a CIA agent who rescues six US diplomats from the Canadian ambassador's residence in Tehran in 1979, paid tribute to real-life agents and diplomats, including the actual character he played.
"Really this award is about Tony Mendez. You saw him. He's an American hero. He represents the (US) foreign service making sacrifices every day for Americans. Our troops overseas. I want to thank them very much," he said.
The movie has been accused of taking liberties with history, notably by exaggerating the role of the CIA in getting the US diplomats out, at the expense of the Canadian envoy in Tehran at the time.
But it was a vindication of sorts for Affleck, who was snubbed in the Oscar nominations announced last week, failing to win a best director nod.
Speaking backstage, George Clooney, a producer on "Argo," admitted he was "disappointed," and that Affleck "should have been nominated" for the February 24 Oscars show. "It's disappointing, but we're not dead yet," he added.
Meanwhile "Les Miserables," a musical adapted from the Victor Hugo book, won best musical/comedy movie, and Australian Hugh Jackman won best actor for his all-singing role, and co-star Anne Hathaway won best supporting actress.
Hathaway won for her portrayal of the young mother and prostitute Fantine, beating fellow nominees Amy Adams in "The Master," Sally Field in "Lincoln," Helen Hunt in "The Sessions" and Nicole Kidman in "The Paperboy."
Day-Lewis, who had been widely expected to win for his turn in "Lincoln," had to make do with being the only big winner for Spielberg's movie -- which has also topped nominations for next month's Oscars.
Former president Bill Clinton provided one of the biggest surprises of the night, taking the stage to pay tribute to Spielberg's movie and to the iconic 16th US president.
"A tough fight to push a bill through a bitterly divided House of Representatives -- winning it required the president to make a lot of unsavory deals ... I wouldn't know anything about that," he quipped.
Tarantino's blood-soaked spaghetti Western tribute "Django Unchained" meanwhile won two Globes: best supporting actor for Austrian Christoph Waltz, and best screenplay for the "Pulp Fiction" director himself.
"This is a damn surprise, and I'm happy to be surprised," said Tarantino, whose film tells the story of a freed slave (Jamie Foxx) who teams up with a dentist-turned-bounty-hunter a few years before the American Civil War.
British songstress Adele, making her first red carpet appearance since giving birth in October, won best song for the theme tune from James Bond blockbuster "Skyfall."
"Hunger Games" star Jennifer Lawrence won best musical/comedy actress for rom-com "Silver Linings Playbook," while best original score went to Ang Lee's "Life of Pi." Scottish-themed "Brave" won best animated feature.
Best foreign language film went to Austrian Michael Haneke's "Amour," which won the Cannes Palme d'Or last year.
On the small screen, terrorism-themed thriller "Homeland" and the quirky Brooklyn hipster comedy "Girls" took top television honors.
"Homeland," which wrapped its second season on the Showtime cable channel last month, won for best dramatic series, as well as best actress and best actor for its two stars, Claire Danes and Damian Lewis.
One of the most intriguing moments of the night came from Jodie Foster.
Receiving a special award, the "Silence of the Lambs" star teased the Globes, hailing her female ex-partner as "one of the deepest loves of my life" -- but then denying she was confirming longstanding rumors that she is lesbian.
"Seriously, I hope that you're not disappointed that there won't be a big coming-out speech tonight, because I already did my coming out about a thousand years ago, back in the Stone Age."
On the red carpet, red was the color of choice for some, including "Silver Linings Playbook" best actress winner Jennifer Lawrence in a strapless gown with a fitted bodice from designer Raf Simons.
Claire Danes, who gave birth just a month ago and won for best dramatic TV actress for "Homeland," opted for a red Versace halter top gown, and "New Girl" Zooey Deschanel donned an equally traffic-stopping Oscar de la Renta creation.
----------------------------------------------------------------------------------------------