Cat Deeley presented the breakthrough act gong to the singer, who appeared to tear-up in an emotional thank-you speech.
She said: "Thank you so, so much. I love my fans. Thank you my fans in the UK, thank you."
The US star also performed at the star-studded show, and was introduced by host Peter Kay as "New York's answer to Sue Pollard".
The outlandish singer donned a huge white wig and mask as she played a low-key version of Telephone on the piano, saying: "This is for Alexander McQueen."
The slow number by Gaga, a massive fan of the designer who recently died, was quickly replaced by a thumping disco beat, as dressed in a hardly-there lace outfit she sang Dance In the Dark.
Jonathan Ross, dressed in a curious mix of a bowler hat and denim, said he had been "pimped" by Dizzee Rascal to present the International Female Artist award.
Lady Gaga looked shocked but thrilled when she heard she had won a second gong.
She walked elegantly up on to the stage, carrying a cup and saucer, to collect her trophy and told the crowd: "I'm so honoured to have these awards."
As she picked up the album gong for The Fame, she could not hold back her tears, and said it was the award that meant the most, because of all the hard work she had put into making the record.
British male solo artist: Dizzee Rascal
International male solo artist: Jay-Z
British group: Kasabian
International female solo artist: Lady GaGa
British female solo artist: Lily Allen
British single: JLS for Beat Again
The MasterCard British Album: Florence And The Machine for Lungs
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