After upsetting South Africa 28-26 on the Gold Coast six days ago, with a Quade Cooper penalty after the siren, the Wallabies' running game shone in the Suncorp Stadium twilight as centre Len Ikitau and winger Marika Koroibete each scored a brace of tries.
Koroibete's second try put the Australians 13 points up with 12 minutes left and they defended brilliantly to turn over the ball in front of their posts twice to protect the lead to the finish.
South Africa managed only one try, through centre Lukhanyo Am shortly after half-time, but drew two yellow cards in a flat performance before they head into back-to-back tests against New Zealand.
"We talked a lot about going back-to-back here," said Australia captain Michael Hooper.
"We absolutely love playing up here in front of the crowd... Couldn't be happier right now."
Australia move up to third in the world rankings ahead of back-to-back tests against Argentina, but South Africa could lose their world number one spot if the Pumas lose to New Zealand by more than 15 points in the late match of the double-header on Saturday.
In a scrappy start, South Africa halfback Faf de Klerk was yellow carded for slowing the ball in a ruck in the 13th minute and Ikitau was quick to capitalise with Australia's first try a minute later.
Australian No.9 Nic White shot a cut-out pass to a charging Ikitau, who beat two defenders in a 10-metre burst to the line.
Barnstorming prop Taniela Tupou then crashed through the South African line, paving the way for a Marika Koroibete off-load that set up Ikitau's second try at the right corner seven minutes later.
De Klerk's return from his 10 minutes in the sin-bin rejuvenated the South Africans as his pinpoint box kicks pressured the hosts.
Wallabies fullback Tom Banks came off clutching his forearm in the 28th minute and his team mate flanker Lachie Swinton came off with a yellow card seven minutes from halftime after a high tackle on No.8 Duane Vermeulen.
Pollard slotted a fourth penalty after Australia were caught offside to trim the lead to 15-12 at halftime.
With Swinton still off the pitch, a De Klerk grubber kick at the right corner allowed Am to touch down and snatch the lead less than two minutes after the restart.
Cooper swiped the advantage back for Australia with his second penalty before Koroibete took control of the game with a two-try burst in six minutes.
Taking an audacious look-away flick pass from Tupou, Koroibete thundered down the left wing for the first of his tries in the 62nd minute.
A Reece Hodge turnover followed by a Samu Kerevi off-load to Pete Samu ended in a brilliant counter-attacking try to Koroibete on the same left wing.
Cooper missed the second conversion but Australia defended solidly to protect the 13-point lead, repelling waves of attacks in their 22 to complete a confidence-building win.