"I am very sorry to announce I won't be able to play at this year's US Open, a tournament in which I've played three consecutive finals in my last participations," he wrote on his official Facebook page on Monday.
A two-time champion in New York, Nadal also missed the tournament back in 2012 as he recovered from a knee injury.
"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," he added.
"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."
The world number two had already been forced pull out of the Toronto and Cincinnati Masters due to the injury he suffered in training last month.
The withdrawal continues an up and down season for the Spaniard as he has failed to match his achievements of 2013, despite claiming a 14th Grand Slam title at Roland Garros back in May.
A back injury bothered the 28-year-old as he lost to Stanislas Wawrinka in the Australian Open final and he was far from his supreme best early on in the clay court season as he suffered surprise defeats to David Ferrer and Nicolas Almagro at the Monte Carlo Masters and Barcelona Open respectively.
He also lost out to world number one Novak Djokovic in the finals of the Miami and Rome Masters, but exacted revenge by preventing the Serb from completing the career Grand Slam with his ninth French Open title.
However, his poor grass court form of recent seasons resurfaced at Wimbledon as he was shocked by 19-year-old Australian Nick Kyrgios in the last 16 in his last outing before being struck down by his latest injury.