The 17-times Grand Slam champion is for the first time missing from Roland Garros in 17 years and has his running streak of 65 straight Grand Slam appearances snapped, Xinhua reported.
"I regret to announce that I have made the decision not to play in this year's French Open," wrote Federer, who made his major debut here in 1999 and also completed his career Grand Slam here in 2009.
The 34-year-old Swiss has been dealing with a series of injuries in 2016, including recovery from knee surgery following the Australian Open and most recently a back injury which forced him out of the Rome Masters a couple of weeks ago.
"I have been making steady progress with my overall fitness, but I am still not 100 percent and feel I might be taking an unnecessary risk by playing in this event before I am really ready," he said.
"This decision was not easy to make, but I took it to ensure I could play the remainder of the season and help to extend the rest of my career.
"I remain as motivated and excited as ever and my plan is to achieve the highest level of fitness before returning to the ATP World Tour for the upcoming grass court season.
"I am sorry for my fans in Paris but I very much look forward to returning to Roland-Garros in 2017," he wrote.
Federer had a 20-minute practice session on Wednesday at Roland Garros' No. 1 court in the hope that he had made a return to full fitness in time for his 68th Grand Slam.