Centuries from AB de Villiers and JP Duminy on Friday gave the Proteas complete control of the match in Port Elizabeth, but left-armer Wayne Parnell's double-wicket maiden put them in the box seat for a victory that would square the three-Test series at 1-1.
Michael Clarke then popped up a simple catch to Dean Elgar in the covers, meaning David Warner (65 not out) faces a mountain of work if his side's to regain equal footing.
Already Warner has chanced his luck, providing an edge that fell just short of de Villiers and another that the wicketkeeper dropped when the aggressive opener was 43.
Nightwatchman Nathan Lyon, whose bowling yielded 5-130 from 46 overs, survived for 37 minutes to be unbeaten on 12.
In the penultimate over of the day Lyon edged Dale Steyn to de Villiers, but the hosts' appeal was turned down and they opted against a review that would have overturned umpire Kumar Dharmasena's decision.
Lyon was then dropped by Duminy at gully in the final over.
De Villiers (116) and Duminy (123) made batting look easy in a 149-run partnership.
Discounting the early lbw dismissal of Chris Rogers to Vernon Philander for five, it was initially a similar story when it came Australia's turn to bat after 150.5 overs in the field.
But things changed dramatically in the 10th over when Graeme Smith first threw the ball to Parnell as the umpires repeatedly checked the light metre.
Playing his first Test in four years, Parnell drew edges from Alex Doolan and Shaun Marsh that flew to wicketkeeper de Villiers.
And with that the 24-year-old, who faced drug charges in Mumbai last year resulting from an IPL party, overtook Mitchell Johnson's match tally of one scalp.
Johnson, Ryan Harris and Peter Siddle bowled a combined 86 overs and were put on ice for the final 18 overs of South Africa's marathon first innings.
All three will need to be managed carefully in the second dig if they're to come up for the potential series decider in Cape Town that starts on Saturday.
It was Australia's longest stint in the field since sending down 154.1 overs against India at Hyderabad in March 2013.
The Proteas added 209 runs to the overnight score before Australia finally wrapped things up with a run-out of Morne Morkel.
Lyon grabbed the key scalps of de Villiers and Duminy to be the pick of the seven bowlers Clarke tried, which included himself.