After winning the first set, the outcome seemed in doubt when Williams blew a 4-1 lead in the second set, allowing Azarenka to storm back and force a final set after winning a tiebreaker.
But in the third, the American star notched a service break for a 3-1 lead, then scored another break and went on to close out her fifth New York title, tying her with Margaret Court and Steffi Graf for the fourth-most all-time.
Azarenka, meanwhile, fell in the U.S. Open final for the second straight year and dropped to 3-13 in her career against Williams.
Williams racked up her ninth victory of the season, improving to 67-4 overall this year.
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