Having slipped down the rankings to ninth and seeded eighth after the withdrawal of Rafa Nadal earlier in the week, the odds of a favourable draw are not in his favour. But should things really go against him, the Scot he could face the possibility of having to beat Jo-Wilfried Tsonga, Milos Raonic, Roger Federer and Novak Djokovic to win the title.
That is a tall order at the best of times but with Murray having flattered to deceive in recent weeks, he knows he has to be on his A-game from the start at Flushing Meadows.
Gael Monfils and Kevin Anderson could be his opponents as early as the third round while the likes of John Isner, who pushed him close in Cincinnati last week, Marin Cilic and Fabio Fognini are others he would like to see in the other half.
As he and his coach, Amelie Mauresmo, who are reportedly enjoying their extended working relationship, begin to taper down training, Murray is focused on ending his year on a high.
Having missed the last three months of 2013 as he recovered from back surgery, he began 2014 with a decent run to the quarter-finals in Australia and, having ended his relationship with coach Ivan Lendl in March, he performed even better at the French Open, where he made the semi-finals.
A surprise defeat by Grigor Dimitrov in the quarter-finals at Wimbledon was a bitter pill to swallow as Murray had been comfortable up to that point, and he has admitted that he is scratching for top form as he heads into the final grand slam of the year.
The good news for Murray is not only that he knows he can win there, as he did in 2012, but that there are question marks over his rivals for the title.
Djokovic, fresh from marriage and soon to be a father for the first time, was off his game in Toronto and Cincinnati, losing early, while Nadal is absent. Roger Federer followed up his runners-up finish at Wimbledon by reaching the final in Toronto and winning Cincinnati but the Swiss, 33, has lost his last two US Opens in the fourth round and quarter-finals.
Murray will also be keeping an eye on events in qualifying, where last night James Ward, Dan Evans and Dan Smethurst were due in first-round action.
John McEnroe's uncompromising advice for the Dunblane man is that he needs to "step up" in New York.
The four-time US Open winner said: "It's difficult to say what's happening with Andy. It's been a process for him to come back from [injury] issues so that takes its toll on the confidence, and he made a big change - I thought he and Ivan worked well together.
"You need to give it more time to judge, but you sort of feel like the US Open would be a time he needs to step up because it's been a struggle compared to what it's been the last couple of years."