Varner, 26, who lost in a three-way play-off in last year's event, fired rounds of 65, 72, 67 and 65 for 19-under 269.
He prevailed in the final round with nine birdies in a seven-under 65 to beat Australian overnight leader Andrew Dodt to win the European Tour co-sanctioned tournament at the Royal Pines Resort.
Dodt, who led for three rounds, finished with a three-under par 69 to take outright second at 17-under 271.
World number seven and 2013 Augusta Masters champion Adam Scott carded his best round of the week, a five-under 67, to finish in third place with 15-under 273.
Varner came closest to winning his first top-level pro event when runner-up after a three-way playoff with Dylan Frittelli and eventual 2015 champion Nathan Holman a year ago.
"I just wanted to find a way to birdie every hole," Varner said. "After last year it feels good back to come back and finish it off."
Varner, ranked 184 in the world, posted four top-10 finishes last season with more than $1.3 million in prize money.
But he said none of that compared to his breakthrough Australian victory.
"Obviously top-10s you get money but it's just hard to win. I don't care where you tee it up ... this is pretty special," he said.
The Aus$250,000 ($186,500) winner's cheque from the Australian PGA triumph also gave him entry to the WGC's Brigestone Invitational next year in his hometown of Akron, Ohio, as well a two-year exemption onto the European Tour.
Varner, starting two shots behind overnight leader Dodt, hit the front on the eighth, but then bogeyed the 14th to go back into a tie for the lead.
However, birdies on the 15th and 17th edged him clear despite Dodt going bogey-free and three under in the final round.
Australian Ashley Hall was fourth on 14-under with compatriot Brett Rumford fifth on 10-under.