GREENSBORO, August 18, 2014 (AFP) - Villegas posted his second seven-under round of the week at Sedgefield Country Club for a 17-under par total of 263.
He finished one stroke in front of Sweden's Freddie Jacobson and Bill Haas. Haas grabbed his share of second with a six-under 64 while Jacobson closed with a 66 for 264.
It was Villegas' first US tour victory since the Honda Classic in March of 2010 and he admitted the long drought has weighed on him.
"I always work hard, I always grind and I love the game, but it starts getting on you and I feel a little lighter right now," Villegas said. "What a great week. I'm happy to be here."
Villegas, who had held the first-round lead after a 63 on Thursday, had fallen back after the second and third rounds and teed of almost an hour before the leaders.
He endured a nervous wait to see if any of those chasing him could at least force a playoff but they all stumbled.
Heath Slocum lost a share of the lead with a bogey at 17, then bogeyed 18 to complete a 67 that left him alone in fourth on 265.
The late hiccup in the US tour's last regular-season event dropped Slocum out of the top 125 in the FedEx Cup standings who advance to the playoff series that starts on Thursday with the Barclays.
Jacobson had a share of the lead at the 18th tee, but also bogeyed the last.
Overnight leader Nick Watney needed a birdie at 18, but was out of bounds off the tee en route to a double-bogey.
He closed with a 70 for 266, sharing fifth place with former champions Brandt Snedeker and Webb Simpson, who both shot 67.
Villegas had four birdies and an eagle on the front nine and added a birdie on the par-five 15th.
That gave him a share of the lead, and he was alone atop the leaderboard after Watney posted a three-putt bogey at the 14th.
"I had a few looks coming in and I thought I needed one more," Villegas said when asked if he thought his score would be enough to win. "Even though that 18th hole is a tough hole, it just happened to work out my way."
In the week's other main storyline -- the race to qualify for the FedEx Cup, England's Paul Casey, who was 125th in the standings coming into the week tied for 18th to safely secure his Barclays berth.
South Korea's Bae Sang-Moon was the only player to move from outside the top 125 to inside on Sunday, finishing in a tie for 14th to move from 126 to 120 and keep his season going.
Leading final-round scores on Sunday in the US PGA Tour $5.3 million Wyndham Championship (USA unless noted, par-70):
263 - Camilo Villegas (COL) 63-69-68-63
264 - Bill Haas 68-66-66-64, Freddie Jacobson (SWE) 68-64-66-66
265 - Heath Slocum 65-65-68-67
266 - Brandt Snedeker 68-65-66-67, Webb Simpson 64-69-66-67, Nick Watney 67-64-65-70
267 - William McGirt 64-68-71-64, Jhonattan Vegas (VEN) 67-65-69-66, Kevin Kisner 69-64-67-67, Brad Fritsch (CAN) 69-63-65-70
268 - Scott Piercy 70-64-69-65, Scott Langley 65-65-69-69
269 - Bae Sang-Moon (KOR) 69-68-66-66, Martin Laird (SCO) 65-66-69-69, Bo Van Pelt 67-65-68-69, Andres Romero (ARG) 70-66-64-69
270 - Carl Pettersson (SWE) 67-65-71-67, David Toms 67-69-67-67, Paul Casey (ENG) 65-69-68-68, DA Points 67-65-70-68, Robert Streb 69-66-67-68, Roberto Castro 71-66-65-68
271 - Luke Guthrie 69-69-68-65, Patrick Reed 71-67-67-66, Francesco Molinari (ITA) 69-67-68-67, Andrew Loupe 65-68-70-68, Tim Clark (RSA) 67-67-69-68, Andrew Svoboda 67-64-70-70, Will Wilcox 67-67-67-70, Ricky Barnes 66-69-66-70