The 50-year-old actor was given the prestigious accolade for his portrayal of stammering British monarch King George VI in `The King`s Speech` and had the audience at Los Angeles- Beverly Hilton Hotel in fits of laughter as he accepted the award.
He quipped: "To get to this stage of your life with your dignity and judgment intact can be somewhat precarious.
"Sometimes all you need is a bit of gentle reassurance to keep you on track but right now this (the award) is all that stands between me and a Harley Davidson."
While Colin was namedBestActor, Natalie Portman received the accolade for Best Actress for her portrayal of a tortured ballerina in `Black Swan`.
The 29-year-old beauty - who is expecting her first baby with fiance Benjamin Millepied - said: "Thank you to my parents for bringing me into this world and giving me this beautiful life. And thank you to Benjamin for helping me to bring more creation into the world."
The `Social Network` - about the creation of the Facebook website - was namedBest Picture in the drama category and also won prizes for Best Director, Best Screenplay and Best Original Score.
TV musical phenomenon `Glee` was namedBest TV Musical or Comedy while two of its stars, Chris Colfer and Jane Lynch, picked up awards for supporting actor and actress respectively.
Other winners at the star-studded ceremony - which was hosted by Ricky Gervais - included Melissa Leo, Christian Bale and Annette Bening.