It is a bitter blow for the Spaniard, who will now miss the competition for the second time in three years, and US Open organisers, who would acknowledge that Nadal is always a huge draw. Yet his absence could help Andy Murray's chances of winning the title for the second time.
The absence of the world No.2 means that Roger Federer will be elevated to second seed behind Novak Djokovic and, on recent form, will fancy his chances of winning the 18th grand slam title of his career. Such a reshuffle also means Murray will be pushed up to No.8 seed - and as such cannot meet any of the top four - or indeed the top eight, before playing in the quarter-finals, That is at least one round further on than had he been ninth seed in line with his current world ranking.
Having taken some time off after Wimbledon, Nadal had hoped to be back for one of the Masters 1000s in Toronto and Cincinnati, not least since the injury was to his right wrist, his non-dominant hand. However, having been unable to hit two-handed backhands in practice without restriction, he will follow medical advice to remain on the sidelines.
"I am very sorry to announce I won't be able to play at this year's US Open a tournament on which I've played three consecutive finals in my last participations," Nadal said in a statement released on his Facebook page and via Twitter.
"I am sure you understand that it is a very tough moment for me since it is a tournament I love and where I have great memories from fans, the night matches, so many things."
Nadal, who will remain No.2 in the rankings unless Federer wins the US Open, is likely to return instead at the China Open late next month, but the 28-year-old was vague when it came to confirming his next outing.
"Not much more I can do right now other than accept the situation and, as always in my case, work hard in order to be able to compete at the highest level once I am back," he said.
Often the seedings do not work according to plan but Murray will surely be relieved that he no longer faces the prospect of drawing, for example, top seed Djokovic in the last 16. After going out in the quarter-finals at Wimbledon, Murray looked strong in Toronto and Cincinnati this month but was beaten in the quarter-finals in both contests, which means the Scot will go into the US Open having not reached a final since he won Wimbledon in 2013.
Having thrown away a winning position in Toronto against eventual winner, Jo-Wilfried Tsonga - the Scot led 3-0 in the final set - and let slip a 4-1 lead in the second set of his defeat by Federer in Cincinnati, there is concern over his match tightness.
Yet Murray knows that a good performance in New York would go a long way to turning his year around and, almost a year on from back surgery, he at least has the fitness to compete for another slam win.