Australia's emphatic 30-13 win over the Springboks in Brisbane on Saturday leaves the South African team all but out of the Tri-Nations title race.
Defending champions South Africa head home with three straight losses, and will need favourable results from Australia and New Zealand to have a chance of retaining their crown.
Flyhalf Will Genia sealed victory with a 75th-minute try after South Africa scored two second-half tries to claw to within 10 points.
Winger Drew Mitchell scored on the stroke of halftime and Matt Giteau slotted five penalties.
The Springboks had a man sin-binned at the start of each half and conceded a raft of first-half penalties to allow the Wallabies to open a 17-3 lead at the break.
Jacque Fourie and Gurthro Steenkamp scored South Africa's first tries after a first half in which they managed only three points from a Morne Steyn penalty.
Steenkamp's try put South Africa within 10 points eight minutes before time.