McIlroy erased a three-shot overnight deficit, firing a final round of four-under par 66 for a 15-under total of 265 and a two-shot win over Garcia.
The 25-year-old from Northern Ireland will overtake Australian Adam Scott atop the world rankings, regaining the number one spot he last held in March of 2013.
Garcia closed with a one-over par 71 on the rain-softened Firestone Country Club Course for a 13-under par total of 267.
His three-stroke lead was gone in the blink of an eye as McIlroy birdied the first three holes and Garcia bogeyed the third to fall one adrift.
McIlroy finished with five birdies and one bogey.
Garcia would pull level going into the back nine, but McIlroy took the lead for good with a birdie at 11.
The Spaniard, who birdied eight of the back nine holes in a 61 on Friday, had his only birdie of the day at the ninth against two bogeys.
Before the drama of the final group played out, defending champion Tiger Woods was the focus of attention as he withdrew after eight holes with back pain that puts his appearance in next week’s PGA Championship in doubt.
The 14-time major champion, who had back surgery in March, said he began suffering from back spasms after landing hard in a bunker after a shot at the second hole. He withdrew after eight holes to bring his third start since his surgery to an abrupt end.