The Springboks made 13 changes to their starting XV for the game, and it showed in a disjointed performance as Australia took full advantage to seal an impressive win over the world champions, though it was closer than it should have been.
South Africa coach Rassie Erasmus will have learnt much from the defeat, as several of his fringe players disappointed, while others who had made a big impact in the 3-1 series win over New Zealand failed to impress off the bench.
Australia were dominant at the breakdown and in the air, two areas where the Springboks generally excel but were second best on the night.
The Springboks took the lead through an early Handré Pollard penalty before Australia replied from the tee through scrumhalf Ryan Lonergan.
The visitors’ forward dominance was evident early on as they scored the opening try from a driving maul.
Hooker Johan Grobbelaar eventually crossed the line after the forwards had done the hard work from a lineout 10 metres out.
Australia took some time to find their attacking rhythm, but after a succession of Springbok penalties allowed them to gain territory, they crossed under the posts through centre Len Ikitau.
The home side carried the ball forward from an attacking lineout, and Ikitau found a gap in the South African defence to stretch over.
Ikitau crossed again in the 27th minute as wing Joseph-Aukuso Suaalii put pressure on Springbok fullback Aphelele Fassi under a high ball.
Neither could gather possession, allowing Ikitau to collect the loose ball and score unopposed.
For almost the first time in the game, the Springboks spread the ball wide, and when centre Canan Moodie ghosted into space, the move ended with wing Edwill van der Merwe scoring his seventh try in eight Tests.
Pollard landed a difficult conversion to level the scores at 17-17 on the half-hour mark, but Australia had the final say in the first half.
Another penalty conceded by the Springboks gave the hosts an attacking opportunity inside the visitors’ 22, and after several phases of pressure, Ben Donaldson crossed out wide.
The Springbok errors continued into the second half and Lonergan landed another penalty to extend Australia's lead to 10 points.
When loose forward Harry Wilson scored Australia's fourth try from close range on the hour mark, the game looked to be effectively over as a contest.
Max Jorgensen added the finishing touch with a fifth try, racing clear following a Springbok handling error to underline just how poor the visitors had been on the night.
South Africa's power in the scrum earned a penalty try and left Australia with 12 men after yellow cards for Wilson, Lonergan and Suaalii in quick succession gave the visitors a sniff.
Morne van den Berg scored from another powerful shove from a five-yard scrum, and when Hunter Paisami received a yellow card for a dangerous tackle on Sacha Feinberg-Mngomezulu, the home side had 11 players on the field.
Ox Nche cross for another Springbok try to make the score 42-38, but they eventually ran out of time to add another try and Australia claimed the win.