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The actress beat Isabelle Huppert (Elle), Ruth Negga (Loving), Natalie Portman (Jackie) and Meryl Streep (Florence Foster Jenkins) to win the award for her role as Mia Dolan in the musical romantic comedy, "La La Land."
"A moment like this is a large confluence of luck and opportunity," the actress said while receiving her award.
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The musical stars Emma Watson alongside Ryan Gosling in lead roles, and follows a musician Sebastian, and an aspiring actress Mia, who meet and fall in love in Los Angeles.
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Gosling who was nominated in the Best Actor category lost to Casey Affleck.
"La La Land" also earned the director Damien Chazelle a best director win.