The 33-year-old world No 21 took a third-round three-shot lead into the final day before he finished on 16 under, one shot ahead of Frenchman Alexander Levy – with three birdies and a bogey either end of his round – to claim his eighth European Tour title.
The win sees the 2010 Open Championship winner move ahead of compatriot Branden Grace and back into fourth place for South African wins on the European Tour, making it six victories in 11 events for the Rainbow Nation this season.
Oosthuizen rued his poor start but was delighted to claim his first win since victory at the Volvo Golf Champions 2014.
He told Sky Sports 4: “I missed the greens on the second and third and was a little rattled after that but I settled in nicely and went back to just hitting greens and giving myself opportunities.
“I love Perth and the golf course. It’s somewhere I would love to come back to. It’s a great course to play.
“It’s been two years since I had a win so this is massive for me going into the season.”
Local favourite Jason Scrivener carded 69 to finish third, with Frenchman Gregory Bourdy and Peter Uihlein of America a further shot back on 13 under.
Oosthuizen saw his three-shot overnight lead quickly cut to one thanks to a bogey on the second as Scrivener and Uihlein made early gains, with France’s Romain Wattel holing a putt for eagle on the third.
South African-born Scrivener had a brief share of the lead after some trouble from a bunker on the seventh but Oosthuizen repeated the trick from the same hazard minutes later to get back in front.
That birdie seemed to spur the eventual winner and he put his tee shot on the par three next to seven feet and rolled in the putt to get to 16 under.
That proved enough for a three-shot lead when Scrivener left his par putt on the ninth short but Uihlein got a birdie and the gap was two shots at the turn.
The trio of Scrivener, Uihlein and Wattel saw their challenges fade on the back nine and, when Oosthuizen put his tee shot to ten feet on the 12th, the lead was extended to four shots.
Levy hit a brilliant second into the 18th to set up a birdie and card a 66, leaving Oosthuizen with a two-shot lead to protect up the stretch, which he did with a bogey on the last.
The Frenchman’s closing round contained eight birdies but was hurt by a double-bogey on the sixth, while a birdie-birdie finish helped Scrivener come home third.
Bourdy, who was right on the cut-line at the halfway stage but went 65-66 over the weekend, finished in contrast to Uihlein, who cut a frustrated figure making a second-consecutive 71.
Allianz EurOpen Strasbourg 2010 winner Wattel finished 12 under, a shot clear of Perth native Brett Rumford, with Singapore’s Mardan Mamat at ten under in eighth.
Elsewhere in Australia, England’s Holly Clyburn finished second, three shots behind South Korea’s Jiyai Shin, in the RACV Ladies Masters on th Gold Coast. The 25-year-old from Cleethorpes finished with a three-under-par round of 70 at Royal Pines Resort.
Scotland’s Pamela Pretswell carded 69 in her fourth round to finish joint eighth.