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McCarthy crowd-surfed to receive her award during the ceremony.
"I may be the first woman to receive this award, but I am certainly not the first one to deserve it," McCarthy said during her acceptance speech. "I'm a walking human patchwork of all the remarkable, funny women I have loved and studied over the years."
She then listed numerous influences, including Lucille Ball, Julia Louis-Dreyfus, Carol Burnett, Gilda Radner, and Whoopi Goldberg.
The actress also thanked her mom, "who taught me not to fear being the butt of the joke, taught me not to worry about being likable or perfect, and to lovingly go for the kill."
She got choked up thanking fans for seeing her movies, and she ended her speech with a shout-out to Bruce Springsteen for getting "even cooler," referring to his cancellation of a North Carolina concert following the passage of the state's anti-LGBT law.
McCarthy is the third person to receive the award. Will Ferrell and Kevin Hart (who cohosted this year's ceremony with Dwayne "The Rock" Johnson) previously won it.
Watch her accept the award below: