The top-seeded Federer and No. 3 Murray were placed in the same section of the field during Thursday's draw at Flushing Meadows for the year's last Grand Slam tournament. Play begins Monday.
Federer beat Murray in July for his record-tying seventh championship at the All England Club; Murray beat Federer this month on the same Centre Court grass for the gold medal.
Second-seeded Novak Djokovic, the U.S. Open's defending champion, could face No. 4 David Ferrer in the semifinals.
Milos Raonic of Thornhill, Ont., will open his tournament with a first-round match with Santiago Giraldo of Columbia.
Rafael Nadal, who owns 11 Grand Slam titles and is ranked third, withdrew with knee trouble that has sidelined him since he lost in the second round of Wimbledon in late June. This is the first U.S. Open since 2008 that doesn't have the quartet of Federer, Djokovic, Murray and Nadal as the top four seeded men, in some order.
The potential men's quarter-finals are Federer vs. No. 6 Tomas Berdych, who upset him in the 2010 Wimbledon quarterfinals; Djokovic vs. 2009 U.S. Open champion Juan Martin del Potro; Murray vs. No. 5 Jo-Wilfried Tsonga; Ferrer vs. No. 8 Janko Tipsarevic.
Possible women's quarter-final matchups are top-seeded Victoria Azarenka vs. defending champion Sam Stosur; four-time major champion Maria Sharapova vs. 2011 Wimbledon champion Petra Kvitova; 14-time Grand Slam title winner Serena Williams vs. former No. 1 Caroline Wozniacki; No. 2 Agnieszka Radwanska vs. No. 6 Angelique Kerber.
Aleksandra Wozniak of Blainville, Que., is set to meet Alexandra Cadantu of Romania in the first round.
Williams' older sister Venus, who is ranked 47th this week and not seeded, plays American wild-card entry Bethanie Mattek-Sands in the first round and could face Kerber in the second. Venus Williams, the 2000 and 2001 champion, pulled out of last year's U.S. Open hours before she was scheduled to play in the second round, revealing that she had been diagnosed with an autoimmune disease.
Four-time major champion Kim Clijsters will begin what she says will be the last tournament of her career against American wild-card recipient Victoria Duval. Clijsters, a 29-year-old Belgian who is seeded 23rd, might face Stosur in the fourth round.
Clijsters won the U.S. Open the last three times she entered the hard-court tournament, in 2005, 2009 and 2010. She missed it last year because of a stomach muscle injury.