The world No 3 was due to compete in Tokyo on the back of his victory at the US Open, where he produced a huge upset to beat Novak Djokovic in the final of the event.
But a back injury has forced Wawrinka to withdraw from the tournament which gets underway on October 3 - the same injury which kept him out of the Olympics, in Rio, during the summer.
It has been a draining month for the Swiss, who lost the final at the St Petersburg Open last week after lifting the US Open crown.
There are question marks now over whether the 31-year-old will appear at the Masters 1000, in Shanghai from October 9 after he has already qualified for the end-of-season Masters, in London.
In Wawrinka’s absence, two-time champion Kei Nishikori will be the No 1 seed in Tokyo, with Gael Monfils, Marin Cilic and Tomas Berdych also in the field.
Nishikori beat Milos Raonic in the 2012 and 2014 finals in front of his home crowd at the Ariake Coliseum.