A one-under 71 was enough to get the world number 21 home on 16-under 272 over Frenchman Alexander Levy after a closing round containing three birdies and two bogeys.
The 2010 British Open champion led by three shots heading into the final round, but briefly lost the lead to Australian Jason Scrivener.
However, birdies at the seventh and eighth holes steadied Oosthuizen as Scrivener fell away with consecutive bogeys on the ninth and 10th.
Oosthuizen had a three-putt bogey at the final hole as he won his first tournament in Australia and his first since the Volvo Golf Championship in 2014.
“It’s great to be back in the winning circle,” Oosthuizen said.
“I always say it’s great to be nervous with three holes to go in a tournament because it means you’re up there somewhere — you’ve a chance of winning it.
“That’s what we do all the hard work for, to try to get into that position.
Louis Oosthuizen's impressive ball striking week. #PerthIntl pic.twitter.com/ZPaiubEtXS
— The European Tour (@EuropeanTour) February 28, 2016
Levy fired the equal-lowest round of the day, a six-under 66, to fall just short of forcing a playoff with 15-under. Scrivener holed a 60-foot putt at the last to finish outright third at 14 under.
Another Frenchman Gregory Bourdy, who only made the weekend cut by one stroke, finished tied for fourth place with American Peter Uihlein at 13 under after closing rounds of 65 and 66.
A third Frenchman Romain Wattel finished with a par 72 for 12 under and outright sixth.
Oosthuizen’s 13th career triumph and eighth on the European Tour continues a successful history of South Africans at Lake Karrinyup tournaments, with Ernie Els (2002) and Retief Goosen (2003) claiming Johnnie Walker Classic wins at the course.
Oosthuizen was the highest-ranked golfer at the Perth International. He was runner-up at the 2012 Augusta Masters, losing at the second play-off hole to American Bubba Watson, and also lost in a play-off at last year’s British Open.
Oosthuizen said he would use his Perth victory to give him momentum heading into this week’s WGC Cadillac Championship in Miami.
