Williams, winner of the last three U.S. women's singles crowns at Flushing Meadows, is followed on the seeding list by number two Simona Halep of Romania, a 2014 French Open finalist.
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Russia's Maria Sharapova, the 2006 U.S. Open winner, is seeded third with 2014 U.S. Open finalist Caroline Wozniacki of Denmark seeded fourth.
Five-times U.S. Open champion Roger Federer is the second seed for the men's event where the top-10 seeds feature five U.S. Open champions and six grand slam winners in all.
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In addition to 2011 champion Djokovic of Serbia and Switzerland's Federer (2004-08), former U.S. champions include Andy Murray (2012), Rafael Nadal (2010, 13) and last year's winner, Marin Cilic of Croatia.
Scotland's Murray is seeded third, Spaniard Nadal is eighth and Cilic seeded ninth. Kei Nishikori of Japan, runner-up last year to Cilic, is seeded fourth, one spot ahead of reigning French Open champion Stan Wawrinka of Switzerland.
Other prominent women's seeds include fifth-seeded Czech Petra Kvitova, the 2011 and 2014 Wimbledon champion, followed at number six by compatriot Lucie Safarova, this year's French Open finalist. Victoria Azarenka of Belarus, a U.S. Open finalist in 2012 and 2013, is seeded 20th.
Twice U.S. winner Venus Williams is seeded 23rd, 2011 champion Samantha Stosur of Australia is 22nd and 2004 U.S. Open champion Svetlana Kuznetsova of Russia is seeded 30th.
A victory for Serena Williams would make her the fourth woman to sweep all four slams in a single season, joining Maureen Connolly (1953), Margaret Court (1970) and Steffi Graf (1988).
It would also be the American's seventh U.S. Open singles crown, breaking her tie atop the all-time list with Chris Evert, and move her into a tie for second on the career grand slam singles list with Graf at 22, two behind Court.
The singles draws for the 2015 U.S. Open will be made at the National Tennis Center on Thursday.
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