Westwood, 45, carded a faultless 64 that included an eagle and six birdies for a tournament total of 15 under-par, three shots ahead of overnight leader Sergio Garcia.
The victory marked Westwood's 24 career win on the European Tour and his 43 worldwide, all of which have come with the #1 ball in golf.
"I was three behind after the third round, knew I had to make a fast start and eagled two", Westwood said after becoming the first European to win three Nedbank titles following 2010 and 2011 triumphs.
"But today showed I have still got it mentally, it was a great performance". Just nice to do it again under pressure and win against a couple of quality players at the end there. "The 7-iron into 17 is probably one of the best shots I've ever hit".
RIGHT: Westwood had his girlfriend, Helen Storey, on the bag for the week at Sun City.
"It's been brilliant. She's caddied twice for me this year and we lost in a play-off in Denmark and we've won here. Might have to have a bit of a rethink, not least about who caddies for me, but our percentages!"
The Spaniard, who had led from the first round into Sunday, could manage only a 70 as his two-shot overnight advantage was swallowed up by a magnificent finish from Westwood.
Westwood made birdies on Nos.
"There's not much more I could have done more", Oosthuizen said.
"It was a great round of golf with the wind moving around and when I looked at the pin-positions last night I saw there were a few smelly ones".
"I played good golf, I attacked nicely and I made a lot of birdies, I made a good run at it".
Garcia has nine wins from his previous 14 54-hole leads on the European Tour and would be the second wire-to-wire victor of the season after Eddie Pepperell at the Sky Sports British Masters. But I'm happy for him, I played as hard as I could but I didn't have my A-game other than the first round and this is a tough course. "I wish I would have won myself, but if not, obviously to see Lee do it is pretty nice". He had a bad Ryder Cup at Hazeltine (in 2016) and he struggled a little bit, but he's been playing much better this year.