McIlory's inability to defend his title in Akron, Ohio not only raised doubts about his chances of playing in the final major of the year, which he won for the second time last August, it also put his top ranking in jeopardy.
American Jordan Spieth, the winner of the season's first two majors, could replace the Northern Irishman at the top of the world rankings if the American wins next week's WGC event.
McIlroy has been out of action since he ruptured a ligament in his left ankle while playing soccer with friends on July 4. The injury ruled him out of defending his British Open title two weeks ago at St. Andrews.
"Unfortunately, I will not be defending my World Golf Championships-Bridgestone Invitational title," McIlroy said in a statement on Wednesday.
"Best of luck to all the competitors and I look forward to returning in 2016."
McIlroy's win at Firestone Country Club last year carried him to world number one, a standing he could lose if Spieth is triumphant in the elite WGC event that runs from Aug. 6-9.
Four-time PGA Tour winner American Chris Kirk has also withdrawn from Firestone. He broke his right hand prior to the British Open while playing with his children.
The PGA Championship, the fourth and final major of the year, will be played at Whistling Straits in Kohler, Wisconsin from Aug. 13-16.
(Reporting by Tim Collings; Editing by Pritha Sarkar/Mark Lamport-Stokes)
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