The world number one, shut out in the first three majors of the year, ended a year of waiting as she joined Chris Evert and Martina Navratilova on 18 majors -- trailing only the 22 of Steffi Graf on the Open era list and six behind the all-time record held by Margaret Court.
Williams, who turns 33 later this month, said the goal of an 18th Grand Slam had hung over her "because I was joining Chrissy and Martina, someone I never thought me, Serena Williams, would be in that name group.
"I never thought you would mention my name with such greats and legends."
Williams lifted the trophy at Flushing Meadows for the third straight year, joining Evert as the only woman in the Open era to win three titles in a row and matching Evert's six US Open triumphs.
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She also offered words of encouragement to her beaten foe, her friend and confidant as both endured difficult months this year.
"Congratulations to Caroline, she knows the struggles I have had," Williams said, adding to her friend: "You will win a Grand Slam title soon."
The Dane was just 19 when she lost to Kim Clijsters in the 2009 US Open final, and she hadn't returned to a Grand Slam title match until Sunday.