Australia need to take six South African wickets on the final day of the third Test to clinch the three-game series after a dominant day four in Cape Town.
The tourists began the day with a lead of 234 runs and extended that to 510 by the time Michael Clarke decided to declare, with David Warner's second century of the match leading the Aussies' second innings.
South Africa knew that batting out the final four-and-a-bit sessions was their best chance of escaping defeat but their second innings got off to a poor start when they lost three quick wickets before tea.
One of those was captain Graeme Smith, whose international career with the Proteas is now over after he was caught off the bowling of Mitchell Johnson for just three.
Following Johnson uprooting Dean Edgar's off-stump with the final ball before tea, Hashim Amla and AB de Villiers played stodgily in the final session but couldn't make it to day five unscathed.
Amla was the man to go when he was trapped lbw by James Pattinson after scoring 41 runs from 109 balls.
South Africa will begin day five on 71-4, 439 runs adrift, with De Villiers (16*) and nightwatchman Kyle Abbott (1*) at the crease.