Thompson had three cuts and a tie for 78th in four previous starts this season, but the overnight co-leader tallied three birdies and an eagle at blustery PGA National on Sunday and closed at 9-under 271 -- good for a 2- stroke victory over the late-charging Geoff Ogilvy, who birdied two of his last three holes for a final-round 69.
"I wanted to just stick to a game plan just like I've been saying all week," Thompson said. "This week was magical, just find a groove, keep believing.
Luke Guthrie shared the lead with Thompson after three rounds, but the rookie carded a 73 and finished alone in third place at 5-under. The 23-year-old was also pursuing his inaugural PGA Tour win.
Two-time heart transplant recipient Erik Compton shot 70 and produced his best finish on the PGA Tour with a tie for fourth at 3-under. He was joined by Keegan Bradley (71), Justin Rose (71), Lucas Glover (70) and David Lynn (69), while Lee Westwood (74), Graeme McDowell (70), Charl Schwartzel (69) and Graham DeLaet (72) tied for ninth at minus-2.
"It's hard for me to get too sentimental about it, because I've turned the corner on my story," said Compton. "I really want to be one of the top 50 players in the world, and I have to the game to do it."
Westwood, who recently moved close to PGA National, finished in the top 10 at this tournament for the third time in the last four years.
Tiger Woods managed a lackluster 74 despite closing his final round with an eagle at the par-5 18th. The world No. 2 shot 70 on each of the first three days, and couldn't produce a repeat of last year's final-round 62, which left him two stokes behind winner Rory McIlroy.
"I just made too many penalties this week," said Woods. "Today is a perfect example. I didn't play that poorly. I had two water balls and a lost ball. Take those away, and I missed two short birdie putts, and it was actually a decent score."
The defending champion and world No. 1 McIlroy wasn't on hand to pursue another title after his sudden and surprising Friday withdrawal. The 23-year- old walked off the course midway through his second round after carding a pair of bogeys, a double bogey and a triple bogey in his first eight holes, later citing a sore wisdom tooth as the cause.
Thompson's previous best finish on the PGA Tour was a tie for second at last year's U.S. Open, where he fired a final-round 67 and hit the clubhouse with the lead, only to watch Webb Simpson charge in front and wrestle away the title.
On Sunday, playing in the final group for the first time, the 27-year-old wrote his own ending.
After taking sole possession of the lead courtesy of Guthrie's bogey on the second hole, Thompson ran home a 49-foot putt across the width of the green on the third for eagle. Guthrie birdied the hole, but Thompson was up by two, and he never relinquished the advantage.
The lead fluctuated but never changed hands over the rest of the final group's outward nine, as Thompson battled the windy conditions to a pair of birdies, a par and three bogeys, and Guthrie bogeyed the fifth before reeling off four straight pars to remain within two.
Guthrie's streak came to an end with a bogey on the 10th, and despite a birdie on No. 13, the rookie dropped out of contention when he hit his tee shot out of bounds on the 14th and settled for double bogey.
Thompson, meanwhile, was wrapping up a stretch of six straight pars on the 15th when Ogilvy flopped a chip onto the green at 16 and watched as the ball curved left towards the hole, hung on the lip, and dropped in to move the 2006 U.S. Open champ within three strokes at minus-6.
Thompson then lipped out a 4-foot par putt on the 16th to fall to 8-under, but he drained one from a similar distance on the next hole to take a 2-stroke lead into the last.
Ogilvy had a chance to pull even at 18 with a tricky and lengthy eagle putt, but he left it inches short and settled for birdie to finish at 7-under.
Needing a par for his maiden win, Thompson dropped his second shot into a greenside bunker, blasted out to within five feet, and drained the birdie putt to seal it in style.
NOTES: Ogilvy parred his first 13 holes on Sunday ... Guthrie spent 2012 on the Web.com Tour, where he posted a pair of victories and seven top-10 finishes in 10 starts. He shot a PGA Tour career-best 63 on Friday to grab the lead. His previous best round was 64 in the last round of the 2012 John Deere Classic and in the third round of this season's Humana Challenge ... McIlroy suffered a cut at the Abu Dhabi HSBC Golf Championship and a first- round loss to Shane Lowry at last week's WGC - Accenture Match Play Championship in his only other starts this season.