“I regret to announce that I have made the decision not to play in this year’s French Open,” Federer wrote on his Facebook page.
“I have been making steady progress with my overall fitness, but I am still not 100% and feel I might be taking an unnecessary risk by playing in this event before I am really ready.”
The 34-year-old world number three, who has been plagued by knee and back injuries this year, last missed a Grand Slam event in 1999 (US Open).
Federer, with his 35th birthday looming in August, has played only four tournaments this year.
Federer’s withdrawal from the French Open, means that nine-time champion Rafael Nadal will be promoted to fourth seed in Friday’s draw behind Novak Djokovic, Andy Murray and defending champion Stan Wawrinka.