Oosthuizen was one shot behind compatriot Branden Grace with two holes to play yesterday, but birdied them both to card a closing 68 and win by one shot on 12 under par.
All seven European Tour events staged at Durban Country Club have been won by South Africans, with eight of the last 11 tournaments in South Africa on by home players.
Oosthuizen has also now started each of the last four calendar years with a victory thanks to a perfect finish after falling foul of the 16th hole for the second day running.
The 31-year-old followed his triple-bogey 7 on Saturday with a bogey 5 yesterday to fall one shot behind Grace, who had birdied two of his last three holes to shoot a 68 and set the clubhouse target.
However, Oosthuizen hit an approach to two feet on the 17th and then chipped to the same distance on the short par-four 18th to seal the win and first prize of £420,000.
Bathgate's Stephen Gallacher ended the first tournament of his 18th professional season looking forward to this week's start of the Tour's 'desert swing', which he hopes will culminate with his defence of the Dubai Desert Classic. However, the Scot failed to break par on any of the four days in Durban, posting a final-round 73 for a four-over-par tally.
"My last two tournaments have been Royal Melbourne (World Cup) and here in Durban, and you won't find too many tougher back-to-back than those," he said. "But it's good to test yourself early in the season as the game is a bit ragged. I played well early on today and overall I am pretty happy, and while my driving is the best part of my game I didn't get to use it that much here in Durban."
Gallacher arrived in Dubai early this morning (Monday UAE time), before making the one-hour drive to Abu Dhabi for Thursday's starting Abu Dhabi HSBC Championship.
Colin Montgomerie began and ended his round with birdies in a score of 76 for a 289 total.
"Nothing to say today. Everything was just awful," said Montgomerie.