Britain's Andy Murray will begin the defence of his US Open title against Michael Llodra of France.
Murray, who is seeded third for the tournament at Flushing Meadows in New York, is in the same half of the draw as world number one Novak Djokovic.
Llodra, 33, is ranked 49th in the world and has been beaten by the 26-year-old Scot in all three previous meetings.
British women's number one Laura Robson, 19, is paired with 32-year-old Lourdes Dominguez Lino of Spain.
Murray last faced left-hander Llodra, a serve-volleyer, at the 2012 Australian Open, when he eased to a straight-sets victory in the last 32.
A potential last-eight opponent could be Czech Tomas Berdych, who beat Murray in the quarter-finals of the Cincinnati Open last week.
Argentine Juan Martin Del Potro, winner of the 2009 tournament, is also in Murray's half of the draw and would be a potential quarter-final opponent for Djokovic, who starts against Lithuanian Ricardas Berankis, ranked 126.
Murray, who arrived in New York last Friday, is relishing the prospect of defending a Grand Slam title for the first time.
"It's obviously tough, it's a new experience for me," he said. "This week has been a bit busier than normal, there's been a few more demands on my time.
"I'm looking forward to it. I want the tournament to get started now. I've enjoyed my tennis the last few weeks, but now it's time for business.
"This is a huge tournament for me. I love this tournament and I'll try to have a good run."
The other half of the draw could see a quarter-final between 17-time Grand Slam winner Roger Federer, seeded seventh, and long-time rival Rafael Nadal, the second seed.
Spaniard Nadal opens against American Ryan Harrison, ranked 97, while Swiss Federer faces Slovenian Grega Zemlja, the world number 61.
Likely semi-final opponents for either Nadal or Federer would be Spanish fourth seed David Ferrer or French eighth seed Richard Gasquet.
In the women's draw Robson, ranked 32nd in the world, is seeded 30th for the tournament.
It is the first time Robson has been seeded for a Grand Slam, and she is the first British woman to be a seeded in such an event since Jo Durie at the 1987 Australian Open.
Robson lost in three sets to Lino, currently ranked 53rd in the world, at the US Open in 2010 in their only previous meeting.
British number two Heather Watson will face fellow 21-year-old Simona Halep of Romania, who is seeded 21st.
Watson has seen her ranking slip to 77 after struggling for form following her recovery from glandular fever.
Top seed Serena Williams plays former French Open champion Francesca Schiavone in the first round and has fellow American Sloane Stephens, who beat her at the Australian Open, as a possible fourth-round opponent.
Second seed Victoria Azarenka takes on young German Dinah Pfizenmaier while Maria Sharapova's withdrawal because of shoulder problems means Agnieszka Radwanska is seeded third and Italy's Sara Errani fourth.