The fourth seed goes into the year's final major, which starts on Monday, as the in-form player of the big four after beating an ailing Novak Djokovic in the final of the Masters 1000 event in Cincinnati last weekend.
It was only the world number one's second defeat in 59 matches this season and the shoulder injury that forced Djokovic to retire in the second set must put a question mark over his chances of winning a third grand slam of the year.
Rafael Nadal and Roger Federer have struggled on the US hard courts so far, with both failing to make it past the quarter-finals in Montreal or Cincinnati.
All of which leaves Murray, a US Open finalist in 2008 and junior champion four years ago, looking in good shape to end his grand slam drought.
Speaking at Thursday's draw, four-time US Open champion McEnroe said: "The hungriest man in the draw should be Murray. I think this is his best shot to win one."
Murray will meet Indian world number 64 Somdev Devvarman for the first time in the opening round and his route to the latter stages is likely to involve clashes with Feliciano Lopez and Stanislas Wawrinka, the man who beat him in the third round 12 months ago.
Robin Soderling or Juan Martin Del Potro are potential quarter-final opponents and for the sixth grand slam in a row Murray finds himself in the same half of the draw as Nadal.
The Spaniard opens the defence of his title against Kazakhstan's Andrey Golubev while world number one Djokovic meets a qualifier and third seed Roger Federer takes on Santiago Giraldo of Colombia.
In the women's draw, all eyes were on where 28th seed Serena Williams would slot in, and the first really big match of this year's tournament is likely to be between the three-time champion and fourth seed Victoria Azarenka in the third round.
Of the three British women who gained direct entry into the main draw - the most for 19 years - Heather Watson was given by far the toughest task with a clash against third seed Maria Sharapova.
British number one Elena Baltacha and Anne Keothavong will both fancy their chances after being drawn against US wild card Jamie Hampton and South Africa's Chanelle Scheepers, respectively.
They could yet be joined by Laura Robson and Naomi Broady, whose second-round qualifying clashes fell victim to the wet weather at Flushing Meadows on Thursday.
There is likely to be much worse to come, with Hurricane Irene heading for New York and predicted to hit the city on Sunday evening.
Speaking at a press conference on Thursday morning, mayor Michael Bloomberg said: "We are reviewing the flood plan for the US Open at Flushing Meadows Corona Park."