The 27-year-old recorded a two-shot victory over Australian Geoff Ogilvy at PGA National in Palm Beach Gardens.
Thompson's surprise win came off the back of a terrible run of form that saw him miss three out his first four cuts this season, hitting rock bottom at his previous outing at the Northern Trust Open.
However, when the US Open runner-up headed out on Sunday morning he was tied for the lead with rookie Luke Guthrie at eight-under-par, with the likes of Lee Westwood, Justin Rose and Rickie Fowler breathing down his neck.
An eagle at the third hole helped settle any nerves and gave Thompson a lead that he never surrendered.
Crucial par saves at the 10th, 11th and 14th helped to steady the ship along the final stretch. However a bogey at 16 and a nervy par save at 17 put him just one shot ahead of Ogilvy going down the last.
After pulling his second shot into a greenside bunker on the par-5 18th, Thompson played his sand shot to four feet, holing the putt for birdie to earn himself a two-stroke victory.
The win now means that Thompson, who was facing up to the prospect of playing on one of the US satellite tours less than two weeks ago, has now earned an exemption on the PGA Tour for the next two years. He also earned himself a place in the final three World Golf Championships in 2013.
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