The world No.3 will kick off his title defence against Michael Llodra at Flushing Meadows and is scheduled to meet the top seed in the semi-finals.
Preparing to defend a Grand Slam title for the first time, Murray, who won his second major at Wimbledon this summer, could also face Tomas Berdych, the man who beat him in Cincinnati last week, in the last eight.
World No.1 Djokovic takes on Ricardas Berankis in his opening match and could face Grigor Dimitrov in the third round, while 2009 champion Juan Martin Del Potro is a likely quarter-final opponent.
Meanwhile, second seed Rafael Nadal, fresh from back-to-back victories in Montreal and Cincinnati, will face Ryan Harrison in the first round. The 2010 champion is seeded to meet John Isner in the fourth round ahead of a possible quarter-final showdown with five-time champion Roger Federer, who drew Grega Zemlja in his opening match.
In the bottom half of the draw, fourth seed David Ferrer can expect potential challenges from the likes of Richard Gasquet, Milos Raonic and Wimbledon semi-finalist Jerzy Janowicz.
Meanwhile, in the women’s draw, Serena Williams will open up against former French Open champion Francesca Schiavone. The world No.1 is seeded to face Angelique Kerber in the quarter-finals, but an all-American clash between Williams and Sloane Stephens, who beat her at the Australian Open, is also on the cards.
Williams is in Agnieszka Radwanska’s half of the draw, while second seed Victoria Azarenka, who opens against Dinah Pfizenmaier, is expected to meet either Petra Kvitova or Sam Stosur in the last eight with Sara Errani a possible semi-final opponent.
British No.1 Laura Robson, who enjoyed a giant-killing run to the fourth-round last year, will face Lourdes Dominguez Lino in the first round, with a potential third-round rematch against Li Na, who she beat at the same stage 12 months ago.