The world number nine withdrew from this week's Masters event in Cincinnati with a right wrist problem and scans have revealed a tear in one of the tendons.
Nishikori is hoping to avoid surgery but joins fellow top-10 players Novak Djokovic and Stan Wawrinka in sitting out the rest of 2017.
It has been a difficult season for Nishikori, who has struggled with wrist issues for several months and has slipped in the rankings from a high of four in March.
A statement from Nishikori's manager read: "Two days ago during practice in Cincinnati, Kei hit a serve and heard a 'pop' in his wrist.
"We went straight to the hospital to take an MRI. Yesterday, we went to see a very renowned wrist specialist who works with many of the MLB baseball pitchers.
"We saw another specialist today to get a second opinion. On top of that we have sent MRI results to three other wrist specialists to ensure we get several independent opinions from specialists.
"After consulting with all of them, it has become clear that Kei has a tear in one of the tendons in the right wrist.
"At this stage we have elected not to do surgery and Kei is in a cast. After the swelling comes down in the next weeks, we will evaluate next steps. Kei will withdraw from all the 2017 tournaments and work hard to be ready for next year."
Nishikori was one of seven top-10 players to miss Cincinnati, joining Djokovic, Wawrinka, Andy Murray, Roger Federer, Marin Cilic and Milos Raonic on the sidelines.
So far only Djokovic, Wawrinka and now 2014 finalist Nishikori have pulled out of the US Open, which starts on August 28.
Their absence leaves Roger Federer as Sky Bet's 11/8 favourite from Rafael Nadal at 11/4, with Murray 9/2 and Alexander Zverev 9/1.
Brazil's Thiago Monteiro replaces Nishikori in the US Open field.
Related links
Sky Bet's latest US Open market
US Open wild card for Sharapova
