"Unfortunately the tear in my left calf muscle needs more time to recover and the timeline is just too short," said Halep, the reigning Wimbledon champion.
Halep sustained the injury in her second-round match at the Rome Open on May 12, and the world number three has deemed the recovery time too tight to be fit for the May 30-June 13 Roland Garros.
"Withdrawing from a Grand Slam goes against all my instincts and aspirations as an athlete, but it is the right and only decision to make," she said.
"The thought of not being in Paris fills me with sadness, but I will focus my energy on recovery, staying positive and getting back on court as soon as it is safe to do so.
"Roland Garros 2022, I'm coming for you A bientot."