First half tries from Ben Alexander and Digby Ioane plus the boot of James O'Connor put the Wallabies in the driving seat at half-time with a 15-6 lead and they opened up in the second half with three more.
O'Connor, Stephen Moore and Adam Ashley-Cooper all crossed, while O'Connor continued his form with the put to rack up a personal haul of 19 points.
Chiliboy Ralepelle and John Smit responded for the Springboks but it was too little too late for Peter de Villiers' side.
Robbie Dean's men were under a huge amount of pressure going into the clash following their loss to Samoa. But boosted by the return of several big guns the Wallabies dominated every facet of the game.
"It was pretty clear that the collisions and contact area won us the game," said Australia captain Rocky Elsom.
"The way we entered the breakdown was really pleasing it put us on the front foot and over the advantage line.
"It gave the backs a lot of space and they were pretty sharp when they had an opportunity. It's great to get off to a good start in the Tri Nations."
Prop forward Alexander grabbed the first try after just 12 minutes. The mercurial Quade Cooper launched the attack from inside his own 22 and following support work from Kurtley Beale and O'Connor the ball was spread wide to Alexander
O'Connor added the extras and a second quick-fire try was scored by Ioane following a break from Will Genia.
Morne Steyn responded with two penalties but that was all the Springboks could managebefore the interval.
The Wallabies came out firing again, first Cooper put O'Connor away for Australia's third try, then Moore hit a Cooper pass to crash through for a fourth.
Cooper was again at the centre of the fifth try as his flip pass sent Ashley-Cooper into space, with Steyn missing a tackle to let the centre flop over the line. O'Connor was once again on target with the extras.
The visitors rallied with Ralepelle being bundled over from close-range, before captain Smit burrowed over in the final minutes.
"We made a bad start and had to chase the game and play catch up rugby which isn't easy in the Tri Nations," said Springboks captain John Smit.
"They attacked us when we were defensively frail. We had chances and when away from home you have to take them.
"But saying that the Wallabies also squandered chances. Both teams will want to improve their accuracy.
"We have to realise how easy it is when you keep the ball and how difficult it is when you don't. We'll take a lot from this and work hard to improve."