Australia moved toward victory by running through the South Africa top order as the tourists chased a world-record winning fourth-innings score of 430 in Adelaide.
The chances of them pulling off the feat looked remote at best as they reached stumps on 77 for four, still 353 runs short of their target.
Nathan Lyon's off-spin did most of the damage as he took two wickets for 15 runs, removing Hashim Amla for 17 and Jacques Rudolph for three.
Openers Alviro Petersen (24) and Graeme Smith (nought) also fell, after the hosts had declared on 267 for eight midway through the fourth afternoon following 54 from Mike Hussey, to leave South Africa with the toughest of asks on the final day.
The tourists' chase suffered an early blow. It was just the sixth ball of the innings when a static Smith edged Ben Hilfenhaus through to Ricky Ponting at second slip for a duck.
Petersen and Amla briefly made life look easy in a second-wicket partnership of 33, sending the ball to the boundary with style and regularity. But it proved to be short lived as Amla nicked one in Lyon's second over and Michael Clarke just about held on at slip.
It could have been worse for the Proteas, but Jacques Rudolph survived the closest of lbw appeals, referred by Australia, two balls later.
Rudolph's reprieve was short-lived, though, as he was caught at short leg by Ed Cowan off another Lyon delivery.
And South Africa slipped to 45 for four when Peter Siddle bowled Petersen off his inside edge.
AB de Villiers, with a painstaking 12 not out from 101 balls, and Faf du Plessis, who was unbeaten on 19 from 74, avoided further loss before the close, but their task looked a forlorn one.