The co-leader after the second and third rounds, Wilson shot 68 to win by two strokes over J.J. Henry.
Henry also shot 68 on Sunday and was alone in second at 269. Kevin Streelman, whose 64 was the low round Sunday, and Heath Slocum (67) tied for third at 270.
Bo Van Pelt, who started the day tied with Wilson, shot 76 to finish at 275 and tied for 15th.
Augusta native Charles Howell (70) and Evans' Vaughn Taylor (69) tied for 38th at 279.
Wilson's bid for a go-ahead birdie on the opening hole rimmed out, but he nailed birdie putts on the next two holes. Two birdies later, he stood on the 13th tee box leading by three strokes. But by the time he tapped in for bogey on 14, his lead over Henry was down to one shot - and the weather was changing, too.
Dark clouds rolled in from the Caribbean Sea and the wind turned stiffer than it had been all week, flapping collars and rippling shirt sleeves .
Henry then bogeyed the 16th and 17th holes, and Wilson bogeyed 16, too. Wilson managed to par 17 about the same time Henry turned up his palms in frustration after the wind swirled his approach to the 18th green.
Wilson had an easy putt to par the final hole and finish at 13-under 267 for the week. He gave a little fist pump, then tipped his cap to the crowd and shared a fist bump with his caddie.
Wilson's only previous victory was at the Honda Classic in 2007, and it took winning a four-man playoff.
But that wasn't even the biggest story of that week. Wilson was on the verge of missing the cut when he took a two-stroke penalty because his caddie told another golfer in the group what club Wilson had hit on a hole, violating a rule about not giving advice. Technically it's Rule 8-1, but it's come to be known as the Mark Wilson Rule.
LPGA tour: In Pattaya, Thailand, Lorena Ochoa won the Honda LPGA Thailand for her 25th career title, easily overcoming an early deficit and pulling away for a three-stroke victory in her season debut.
The top-ranked Mexican star, three strokes behind playing partner Paula Creamer at the start of the round, shot 6-under 66 in overcast conditions that took the edge off the heat at the Siam
Country Club's Plantation Course.
Ochoa finished at 14-under
274 - shooting 71-69-68 the first three days - and earned $217,500 for her second consecutive season-opening victory. Last year, she opened with a victory in Singapore in the HSBC Women's Champions and went on to win five of her first six events. She will be in Singapore next week for her title defense.
South Korea's Hee Young Park shot 65 to finish a career-high second. The third-ranked Creamer had 73, leaving her four strokes back at 10 under.
Stacy Prammanasudh, an American who has a Thai father, shot a course-record 63 to tie for fourth with Brittany Lang (73) at 7 under.
European/asian tours: In Bali, Indonesia, Thailand's Thongchai Jaidee won the Indonesia Open for his record 11th Asian Tour title and first European Tour win in four years, closing with 3-under 69 for a two-stroke victory.
Thongchai, who is ranked 88th in the world. broke a tie with compatriot Thaworn Wiratchant for the Asian Tour's victory record, finishing at 12-under 276 on the New Kuta Golf Club course.
Englishmen Steve Webster (68) and Simon Dyson (69) and Sweden's Alexander Noren (70) tied for second.
Nationwide tour: In Fingal, Australia, Alistair Presnell won the Moonah Classic , birdieing the 18th hole for 4-under 68 and a one-stroke victory over fellow Australian Peter O'Malley.
The 29-year-old Presnell finished at 9-under 279 on the Moonah Links course . He earned $108,000 and full Nationwide Tour status for the rest of the season.
O'Malley bogeyed the 17th en route to 70.
Australia's Michael Sim (70) was third, three strokes behind. Americans Skip Kendall (70) and Daniel Summerhays (72) finished at 5 under along with Australians Terry Pilkadaris (70) and Adam Bland (71).