Serena Williams' quest for a record 23rd Open era Grand Slam title starts against Russia's Ekaterina Makarova, while Novak Djokovic begins his U.S. Open title defense against Jerzy Janowicz.
Play begins Monday in the final major tennis tournament of 2016. First-round pairing were set Friday, two days after the top 32 seeds in men's and women's brackets were announced.
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Williams lost in the semifinals of last year's competition at the USTA Billie Jean King National Tennis Center in New York.