Australia recovered from their surprise defeat to Samoa last week with an assured 39-20 victory over South Africa in the 2011 Tri-Nations opener.
The Wallabies set about making amends with tries from Ben Alexander and Digby Ioane inside 12 minutes.
Two penalties from Morne Steyn helped steady the Springboks but James O'Connor racked up 14 second-half points to drive Australia to victory.
New Zealand take on South Africa in the tournament's second match on 30 July.
The Tri-Nations takes a shortened six-match format this year, with the final match just two weeks before the start of September's World Cup.
South Africa coach Pieter de Villiers had been forced to field a side packed with players who are likely to be on the fringes of the squad for the year's showpiece event after a run of injuries and they were given little time to settle by the hosts.
A mazy run from fly-half Quade Cooper, recalled after being rested in the wake of Queensland's Super 15 success, set up a tremendous try for prop Alexander before Ioane dotted down straight from the restart.
Australia squandered several other openings as James Horwill spilled the final pass of a sweeping counter-attack with the line beckoning.
But the hosts made their pressure tell after the break as Cooper darted through to send the 21-year-old O'Connor over and Stephen Moore cut an angle to gather the try bonus point for his side.
Another skilful off-load from Cooper created the fifth try as he flipped a pass to Adam Ashley-Cooper in space.
A pair of short-range tries from South African front-rowers Chilliboy Ralepelle and captain John Smit lessened the damage for the visitors but were never likely to change the result.
Australia: Kurtley Beale; James O'Connor, Adam Ashley-Cooper, Pat McCabe, Digby Ioane; Quade Cooper, Will Genia; Ben Alexander, Stephen Moore, Sekope Kepu, James Horwill, Rob Simmons, David Pocock, Rocky Elsom, Ben McCalman. Replacements: Saia Fainga'a, Pek Cowan, Nathan Sharpe, Matt Hodgson, Scott Higginbotham, Nick Phipps, Anthony Fainga'a.
South Africa: Gio Aplon; Bjorn Basson, Juan de Jongh, Wynand Olivier, Lwazi Mvovo; Morne Steyn, Ruan Pienaar; Werner Kruger, John Smit, Dean Greyling, Johann Muller, Flip van der Merwe, Danie Rossouw, Deon Stegmann, Ashley Johnson. Replacements: Chiliboy Ralepelle, CJ van der Linde, Alistair Hargreaves, Jean Deysel, Charl McLeod, Adrian Jacobs, Patrick Lambie.