Webb beat Ai Miyazato by one stroke after starting the day at Royal Pines four behind the 19-year-old from Japan, who led the joint Australian and European Ladies Tour event after each of the first three rounds.
But Webb birdied the second hole, chipped in for eagle on the par-5 third from about 60 feet and then birdied the fourth to pull into a tie for the lead.
'That was an added bonus,' Webb said of the eagle. 'I was just hoping to get that one up and down. It was nice to see it go in.
'It's a great start to the year and will give me some confidence, hopefully to take back to the States with me.'
The Australian finished at 16-under 272. Miyazato closed with an even-par 72.
After the chip-in, Webb and Miyazato dueled most of the rest of the way, both making birdies on the par-5 ninth to make the turn tied.
Webb went ahead by one with a 12-foot birdie putt on the 13th hole, knocking Miyazato out of the lead for the first time since Thursday.
Miyazato then three-putted the par-3 14th to give Webb a two-stroke lead that was reduced to just one when Webb bogeyed 18 after hitting into a greenside bunker.
Miyazato, who hit her drive into a fairway bunker, just missed a birdie putt of about 25 feet that could have forced a playoff.
'I played very well today but I couldn't get the putts to go in,' Miyazato said. 'I'm not disappointed with my week.'
Webb made a 3-footer for her bogey on the 18th, then threw her arms into the air when the ball rolled into the back of the cup.
'I think I'm pretty lucky to get one off her now because in a few years we'll be seeing her in the winner's circle more and more,' Webb said of Miyazato.
It was Webb's first victory since winning the LPGA Tour's Kellogg-Keebler Classic last June in Aurora, Illinois, her 30th career win.
Maria Hjorth of Sweden (69 Sunday) and Veronica Zorzi of Italy (70), finished tied for third at 12-under 276.
Miyazato, who won five tournaments on the Japanese tour last year after turning pro, equaled Webb's course record of 9-under 63 in the first round. Webb set the mark while winning the tournament in 1999, her second of four Masters wins in a row.
Annika Sorenstam ended Webb's streak in 2002 with the first of her two wins at Royal Pines. In her 12 appearances here, Webb has also finished second four times and been outside the top 10 just once.
It was a solid return to form for Webb. In 2002, Webb became the youngest player to complete a career Grand Slam, and last year she passed $10 million in prize money on the LPGA tour.
In the last three years, she has been replaced by Sorenstam as the leading player in women's golf.
American amateur Tiffany Joh, who also equaled the course record on Saturday, finished with a 72 Sunday for a 7-under total of 281 and tied for 13th, nine back of Webb.
England's Laura Davies, a three-time Masters champion, had a final-round 74 and tied for 48th.