Flushing Meadows has seemed the most likely destination for the world number four's major breakthrough ever since he clinched the junior title as a 17-year-old in 2004.
Four years later he reached his first grand slam final, losing in straight sets to Roger Federer, but since then it has proved a much less happy hunting ground, with premature defeats in both the last two years.
Twelve months ago he lost in four sets to Stanislas Wawrinka in round three, capping an inconsistent season where he seemed to stand still.
This year has had its moments as well but there is no doubt Murray has taken another step forward, and he has reserved his best for the biggest tournaments, reaching the final of the Australian Open and the semi-finals of the French Open and Wimbledon.
The 24-year-old also goes into the year's final grand slam as the man in the best form out of the top four after his victory in the Cincinnati Masters last week.
Rafael Nadal and Roger Federer have struggled on the hard courts so far this summer while there were signs in Cincinnati, even before he withdrew during his final clash against Murray through injury, that Novak Djokovic's incredible season may be catching up with him.
The Serb's shoulder injury is unlikely to prevent him playing at Flushing Meadows but, after 57 wins from 59 matches in 2011, the feeling is this may be one tournament too far.
Murray may therefore lean towards favouring Djokovic's half of the draw, if only to ensure there is no possibility of a third successive grand slam semi-final against Nadal following victories for the Spaniard in Paris and at Wimbledon.
In-form American Mardy Fish, the top home player in the seedings for the first time at number eight, appears the player most likely to break the big four's dominance.
In the women's draw, Caroline Wozniacki is once again the top seed despite a poor summer while 28th seed Serena Williams is certainly the player everyone will be hoping to avoid, along with her unseeded sister Venus.
Meanwhile, British pair Laura Robson and Naomi Broady will both be hoping to reach the final round of qualifying after recording straight-sets victories in round one on Wednesday.
Robson, who has fallen just short for the past two years, next faces 15-year-old home hope Taylor Townsend while Broady has a tricky task against 22nd seed Chang Kai-chen.
There was disappointment last night, though, for James Ward, who has risen to a career-high ranking of 139th this month but slipped to a 7-6 (7/2) 6-4 defeat by American Michael Yani.