The third seed faces Russia's Alex Bogomolov in the second match on the Arthur Ashe Stadium on the opening day.
The Briton, 25, is seeking to win his first major, having finished runner-up to Roger Federer at Wimbledon.
"I feel confident in myself just now. That's what's important," said Murray, who reached the US Open final in 2008.
"Winning the Olympics was the biggest win of my career, that's for sure. It meant a lot to me.
"But you never know what's going to happen when you get out there on the court. I've prepared well and trained hard, so I'm ready to go."
Murray suffered a fourth consecutive Grand Slam final defeat when
he lost in four sets to Federer at Wimbledon,
but made up for that by defeating both Novak Djokovic and Federer in consecutive straight-set victories at the Olympics.
"I didn't really play much in Toronto, so I do not think it's going to have much bearing at all," he added.
"I went into Wimbledon this year having lost in the first round of Queen's. That was meant to be a horrible preparation, but Wimbledon worked out fine. So there's no reason why that can't happen here."
Murray's best in Grand Slams
F (2010, 2011)
Two of Murray's fellow Britons,
are also in action on day one, with
in action on Tuesday.
Watson takes on Chinese ninth seed Li Na in the first match on Court 17 and Robson plays American Samantha Crawford in the third match on Court Four.
The 31-year-old, whose success at Wimbledon in June was his first Grand Slam title in nearly two years, has pushed himself back to the top of the
men's world rankings.
Federer, who starts his campaign on Monday against Donald Young, remains the favourite to claim a sixth US Open title and his 18th Grand Slam crown.
"I feel like if I'm playing well I can dictate who's going to win or lose," Federer said.
"It's going to take something special from my opponent to win. That's kind of how it feels right now; then again, I might walk away from Monday and lose in the first round. I will take it one match at a time."
In the opposite side of the draw is world number two and defending US Open champion Djokovic.
Other big names to follow
Former champions Kim Clijsters and Maria Sharapova, 2011 winner Sam Stosur, world number one Victoria Azarenka and former Wimbledon champion Petra Kvitova are also in action on the opening day
The 25-year-old, who has been handed a comparatively easy draw to that of Murray and Federer - following
the absence of Spaniard Rafael Nadal
with an knee injury - has only won one title in the last four months.
The Serb has struggled to produce the same form of this successful 2011 season, which saw him climb to world number one and claim three of the four Grand Slam titles, but he remains confident with the task in hand.
"It's hard to compare with 2011, but I actually try to always look from a positive side," Djokovic said. "I do feel physically stronger and more prepared than last year. Mentally I had some ups and downs throughout the season, but I think that was maybe expected."
He said he hoped to be inspired by the famously raucous crowd at Flushing Meadows. "I feel this energy, and I love playing in this tournament. You definitely can feel that.
"Especially the night matches that you play as a player here and in front of the packed stadium. It's a lot of entertainment, a lot of fun.
"Fans get into every point, they play with you, so it's quite different from all the other tournaments."
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