Her old sparring partner Elton John declared that Madonna didn't "have a chance of winning" a Golden Globe.
When a reporter suggested "those were fighting words," he replied: "No, those are accurate words."
But the Queen of Pop had the last laugh.
She beat Elton to the trophy for best original song. Masterpiece, the tune she wrote for W.E,. her film about Wallis Simpson, was recognised over his effort Hello Hello from Gnomeo and Juliet.
Later acerbic compere Ricky Gervais made her the target of his quips.
He mockingly introducing her as still "Like A Virgin", but Madonna had a quick-witted riposte.
Firing back, the singer challenged him: "If I'm just like a virgin, Ricky, why don't you come over here and do something about it" â€“ before adding a jibe about his masculinity, quipping: "I haven't kissed a girl in quite a few years, at least not on TV".
He raised a few laughs by pretending to be frightened and darted off the stage behind her.
On top of the critical acclaim for her professional endeavours, Madonna was also a winner in thestyle stakes.
She looked great as glittered on the red carpet in an eye-catching green and metallic creation from Reem Acra.
Madonna Wins Best Song at Golden Globes, Jabs 'Girl' Ricky Gervais
1:25 AM PST 1/16/2012 by Marc Schneider, Billboard
"Masterpiece" from "W.E." beat out Elton John's "Hello Hello" (from "Gnomeo and Juliette") and Mary J. Blige's "The Living Proof" (from "The Help").
"Masterpiece," a ballad co-written and sung by Madonna for her new film W.E., earned the best original song Golden Globe at the glitz-filled awards gala on Sunday. It was the second Globe for the director-singer, who won for best actress in a comedy or musical in 1997 for Evita.
With her slight British inflection, Madonna made sure to thank her longtime manager, Guy Oseary, "for being so irritating." And studio boss Harvey Weinstein, whom she called "the punisherâ€¦ for believing in my film. Thank you for my film."
Later, when introducing the best foreign language film, she had a poke at host Ricky Gervais (who joked she remains "just like a virgin").
"If I'm still just like a virgin, Ricky. Then why don't you come over here and do something about it," she said with a smile. "I haven't kissed a girl in a few years. On TV."
Madonna's "Masterpiece" is a moody ballad featuring a simplified production reminiscent of her sound in the 1990s, while the lyrics lean on the emotional side and tie into the film's love story. It was co-written by James Harry.
Starring James D'Arcy and Andrea Riseborough as King Edward VIII and his lover Wallis Simpson, W.E. tells the story of when the monarch abdicated his throne in 1936 to marry the twice-divorced American.
The song was not short-listed for the best original song Oscar and reviews for the film have been mixed. It beat out Elton John's "Hello Hello" (from Gnomeo and Juliette) and Mary J. Blige's "The Living Proof" (from The Help) to win the Globe.
In the original score category, Frenchman Ludovic Bource (The Artist) bested Trent Reznor andAtticus Ross, who were angling to repeat last year's win, for The Social Network, with David Fincher's The Girl With the Dragon Tattoo. Reznor seemed to take the loss in stride, tweeting seconds after the envelope was opened, "HOLY SHI (oh, nevermind!)."
The 'Rocket Man' singer called his young protege to wish him well after it was revealed he leads this year's awards with four nods last Thursday (12.01.12).
Ed told The Sun newspaper: "I speak to Elton on a weekly basis. He's very involved. I got a talk from him after the BRITs nominations.
"He's overseas at the moment but left me an answer phone message. He said I've smashed it so hard and good luck.
"It's always good to hear from Elton. He's a lovely guy and is very passionate about the music. He wants me to be huge all over the world, and I'm up for that too."
'A Team' singer Ed is very driven when it comes to his career, and didn't even stop for long over Christmas, instead opting to fly to the US to record tracks with a top rapper.
He added: "I got home for Christmas and it was lovely to see my friends and family. Then I got the email from this rapper so I went. I get restless when I'm not creating.
"I'm 20 and have a lot of steam to burn off so I keep going. I don't have much time for a love life though. I had a relationship from school but I realised that didn't work and that I'd have to be married to my job for a few years."
Ed is nominated for Best Male Solo Act and Best Breakthrough Act at the BRITs, while his debut album, '+', is up for Mastercard British Album of the Year and his single 'A Team' is one of the nominees for Best British Single. The awards will take place on February 21 at The O2 venue in London.
Golden Globes 2012: See the full list of winners here
Madonna shocked Sir Elton John by winning the best original song, Meryl Streep won best actress in a drama for her portrayal of Margaret Thatcher and George Clooney took the best actor award home, to put in his toilet, or something.
Hereâ€™s who else won what at the 69th Golden Globe Awards:
Film Picture, Drama: The Descendants.
Picture, Musical or Comedy: The Artist.
Actor, Drama: George Clooney, The Descendants.
Actress, Drama: Meryl Streep, The Iron Lady.
Director: Martin Scorsese, Hugo.
Actor, Musical or Comedy: Jean Dujardin, The Artist.
Actress, Musical or Comedy: Michelle Williams, My Week With Marilyn.
Supporting Actor: Christopher Plummer, Beginners.
Supporting Actress: Octavia Spencer, The Help.
Foreign Language: A Separation.
Animated Film: The Adventures of Tintin.
Screenplay: Woody Allen, Midnight in Paris.
Original Score: Ludovic Bource, The Artist.
Original Song: Masterpiece (music and lyrics by Madonna, Julie Frost, Jimmy Harry), W.E.
Television Series, Drama: Homeland, Showtime.
Series, Musical or Comedy: Modern Family, ABC.
Actor, Drama: Kelsey Grammer, Boss.
Actress, Drama: Claire Danes, Homeland.
Actress, Musical or Comedy: Laura Dern, Enlightened.
Actor, Musical or Comedy: Matt LeBlanc, Episodes.
Miniseries or Movie: Downton Abbey (Masterpiece), PBS.
Actress, Miniseries or Movie: Kate Winslet, Mildred Pierce.
Actor, Miniseries or Movie: Idris Elba, Luther.
Supporting Actress, Series, Miniseries or Movie: Jessica Lange, American Horror Story.
Supporting Actor, Series, Miniseries or Movie: Peter Dinklage, Game of Thrones.
Cecil B. DeMille Lifetime Achievement Award: Morgan Freeman.