Hashim Amla's 93 not out helped extend South Africa's lead to 369 with six second-innings wickets intact after day three of the second Test against South Africa in Port Elizabeth.
Amla hit 12 fours in his 126-ball effort as South Africa closed on 192-4 in their second innings having bowled Australia out for 246 to claim a first-innings advantage of 177 earlier in the day.
Seamers Vernon Philander (3-68) and Morne Morkel (3-63) did the damage, Australia slipping from an overnight 112-4 to 168-7 before Steve Smith's 49 at least got them above 200.
David Warner, on 65 at the start of the day, was first to go in the fifth over of the morning after adding only five runs to his total, edging a big drive to Graeme Smith at first slip to give Philander the breakthrough.
Nightwatchman Nathan Lyon (15) played a short ball from Morkel onto his stumps after a working over and Dale Steyn (1-55) beat Brad Haddin's drive with an inswinger to send him on his way for nine and leave Australia reeling.
Smith and Mitchell Johnson counter-attacked during an eighth-wicket stand of 37 which ended on the stroke of lunch with Johnson (27) being bowled through the gate by JP Duminy's spin in the over after Morkel had hit him on the helmet.
Morkel finished the innings off in early afternoon, Smith nicking through to wicketkeeper AB de Villiers and Ryan Harris edging to Faf du Plessis at second slip after a run-a-ball 26.
South Africa stumbled early in their second innings, Johnson removing home skipper Smith (14) for the third time in four innings and Dean Elgar (16) edging to wicketkeeper Haddin off Peter Siddle's bowling.
But Amla was in fluent form and received support from Du Plessis (24) and De Villiers (29) during a pair of half-century stands that took South Africa's lead beyond 300 in the evening session.
By the close, that had become 369, already more than has ever been achieved in a successful Test run chase on South African soil.
Australia lead the three-match series 1-0 after a Johnson-inspired, 281-run win at Centurion last week.