The pair will be joined by Americans Venus Williams and Andy Roddick in playing their opening matches on the Arthur Ashe centre court.
Switzerland's Roger Federer and Belgian Kim Clijsters are among five former champions in action on a busy opening day at the US Open on Monday.
The pair will be joined by Americans Venus Williams and Andy Roddick in playing their opening matches on the Arthur Ashe centre court while another former champion, Australian Lleyton Hewitt, begins his campaign on the Louis Armstrong stadium.
Federer won the men's championship five times on the trot from 2004 to 2008 but will not start the event as the defending champion after his loss to Argentine Juan Martin Del Potro in last year's final.
Del Potro is absent this year because of injury but another Argentine, Brian Dabul, will be in the spotlight when he faces Federer in the first round.
"Maybe there is an extra incentive for me to try to win it again after being two points away last year," Federer told reporters.
"It was a disappointing loss for me, I felt like that was one of the finals I should never have lost.
"At the end Del Potro played great and deserved the victory. It was a tough one to swallow."
With Del Potro away, Clijsters is the lone defending champion. She plays Hungarian Greta Arn first up.
Clijsters won in 2005 but did not get the chance to defend her title in 2006 because of injury. She missed the event in 2007 and 2008 after taking time out to start a family before a fairytale return last year.
"I'm so excited to be back to defend my title. This is a first for me," she said.
Roddick, who won his only grand slam title at New York in 2003, has been plagued by illness in recent months but the prospect of returning to the centre court has given him a boost.
He plays Frenchman Stephane Robert in his first match which coincides with his 28th birthday.
"Birthday or no birthday, you come in to try to win one," he said.
"I don't think too much about age, numbers, whatever. I'll play til I can, until I feel like I shouldn't anymore."
Williams, who will fly the family flag after her sister Serena withdrew because of a foot injury, won the US Open in 2000 and 2001 and was runner-up in 1997 and 2002, has also been troubled by injuries but said she was fit and raring to go in her first match against Italian Roberta Vinci.
"Theoretically I've had more rest than everyone, I should be fresh," Williams said.
Hewitt, who won here in 2001, is one of two Australians in action at Louis Armstrong Stadium. He plays Paul-Henri Mathieu of France after Samantha Stosur, this year''s runner-up at the French Open, faces Elena Vesnina.
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