Should the seedings go to plan, the pair will be squaring up for real in the quarter-finals, just two years on from Murray's triumph over the Serb to secure his first grand slam title.
Neither man will have been too impressed with the hand he was dealt as they landed in by far the trickier half of the draw, but Murray's path to another final is littered with huge obstacles.
After opening up against the Dutchman Robin Haase, he could face Radek Stepanek and Fernando Verdasco before taking on Jo-Wilfried Tsonga in the last 16, all before a probable quarter-final with the world No.1. Should he make it past those five, he might have to face the Australian Open champion Stan Wawrinka in the semi-finals and another Swiss, the second seed, Roger Federer in the final.
Five-time champion Federer must have thought it was all his birthdays rolled into one when he saw a kind draw, although Grigor Dimitrov could await him in the quarter-finals.
Of course Murray will know that, in one way, he has only himself to blame for his predicament, having dropped to No.9 in the rankings. Seeded eighth, as a result of the withdrawal of the defending champion, Rafael Nadal, Murray was denied the protection of being among the top four and, if the seedings do pan out, is certainly up against it.
Brad Gilbert, his former coach, described it on Twitter as a "brutal draw" but the one good thing for Murray is that he will have to hit the ground running and cannot afford any let-up in the first week if he wants to be around in the second.
In Cincinnati last week, when he let slip a 4-1 double-break lead over Federer in the second set of their quarter-final, and in Toronto the week before that when he led Tsonga 3-0 in the final set of their last-eight tie, Murray has shown a worrying lack of intensity in finishing the job.
The 27-year-old left Cincinnati frustrated by his lack of focus but a grand slam usually has him on message and he knows all about the world No.70 Haase, having come from two sets down to beat him in the second round in New York in 2011.
Two Englishmen, Dan Evans and Dan Smethurst, went out on round one of qualifying on Wednesday, leaving James Ward as the only one with a chance to join Murray in the main draw. Evans, who qualified and reached the third round last year, had a match point but went down in three sets to Jimmy Wang while Smethurst was well beaten by the Russia's Konstantin Kravchuk.
Ward, ranked a career-high 131 after some impressive performances of late, was due to play France's Vincent Millot last night for a place in the final round of qualifying.
Serena Williams helped conduct the draw yesterday but will not be relishing her first-round encounter against rising star Taylor Townsend. The world No.1, who has won the past two US Open titles, has not made it to the last eight of any of the grand slams this year, despite dominating the regular Tour. "The way my year's been going, I'm worried about every single match," Williams said, before heading off to a TV appearance on the David Letterman show.
Britain's lone woman in the main draw, Heather Watson, takes on Sorana Cirstea of Romania in round one, with Eugenie Bouchard likely to be waiting in round two.