Australia were 159 for eight when bad light ended play three overs early with Steve Waugh 34 not out and Brett Lee on five.
The tourists scored 315 in their first innings after being put in to bat, to which South Africa replied with 167.
South Africa resumed on 48 for one and lost their second wicket in the eighth over of the day when nightwatchman Paul Adams, on six, fell to a stunning one-handed catch by Matthew Hayden in the gully off fast bowler Lee.
Six balls later, Graeme Smith played away from his body to a delivery from fast bowler Glenn McGrath and was caught behind by wicket-keeper Adam Gilchrist for one.
Herchelle Gibbs got his 50 with a sublime drive off the back foot through the covers for four off Lee, but he faced just seven more balls and added one run before edging an outswinger from fast bowler Jason Gillespie.
Six overs before lunch, Jacques Kallis attempted to play a lofted drive to Shane Warne, but offered the leg spinner a simple return catch instead to be out for 16.
South Africa went to lunch on 115 for five, and they were dismissed 18 overs into the second session having lost their last five wickets for 48 runs.
Warne dismissed Ashwell Prince and Mark Boucher in the space of five deliveries, both without scoring and both to full tosses.
Prince pulled a delivery to mid-on, while Boucher attempted to work the ball to the leg side and sent a leading edge looping back to the bowler.
Neil McKenzie was then brilliantly caught by Damien Martyn, leaping high at point, off Lee for 25, while Andrew Hall was 27 not out.
Warne was not at his best but finished with four for 33, while Lee was successful but veering towards expensive in taking four for 82.
Australia’s batting problems began in the second over, when fast bowler David Terbrugge had Hayden caught at cover by Prince for a rare duck.
Terbrugge struck again in his next over when Justin Langer was caught behind by wicket-keeper Boucher for 18.
Ricky Ponting and Mark Waugh dug in to share 58 runs for the third wicket, but Australia then lost five wickets for the next 52 runs.
Three of them fell to fast bowler Kallis, who delivered his most penetrative bowling of the series so far in taking three for 18 in a spell of eight overs.
Kallis bowled Waugh off his pads for 30, had Martyn caught behind without scoring, and dismissed Gilchrist in similar fashion with a fine away swinger for 16.
Five overs before the close, Gillespie lunged at a googly from left-arm wrist spinner Adams and was well held at first slip by Kallis for three.
AUSTRALIA (1st Innings) 315 (A.C. Gilchrist 91, R.T. Ponting 89).
SOUTH AFRICA (1st Innings, overnight 48-1):
H.H. Gibbs c Gilchrist b Gillespie 51
G. Kirsten c Gilchrist b Lee 21
P.R. Adams c Hayden b Lee 6
G.C. Smith c Gilchrist b McGrath 1
J.H. Kallis c and b Warne 16
N.D. McKenzie c Martyn b Lee 25
A.G. Prince c Lee b Warne 0
M.V. Boucher c and b Warne 0
A.J. Hall not out 27
M. Ntini c McGrath b Warne 14
D.J. Terbrugge c Gilchrist b Lee 0
EXTRAS (LB-1, W-1, NB-4) 6
TOTAL (all out, 55.2 overs) 167
FALL OF WKTS: 1-48, 2-74, 3-75, 4-85, 5-109, 6-119, 7-119, 8-148, 9-167.
BOWLING: McGrath 11-4-26-1 (1nb); Lee 17.2-1-82-4 (1nb, 4w); Gillespie 14-6-25-1; Warne 13-4-33-4.
AUSTRALIA (2nd Innings):
J.L. Langer c Boucher b Terbrugge 18
M.L. Hayden c Prince b Terbrugge 0
R.T. Ponting c Terbrugge b Ntini 34
M.E. Waugh b Kallis 30
S.R. Waugh not out 34
D.R. Martyn c Boucher b Kallis 0
A.C. Gilchrist c Boucher b Kallis 16
S.K. Warne c McKenzie b Adams 13
J.N. Gillespie c Kallis b Adams 3
B. Lee not out 5
EXTRAS (LB-3, W-1, NB-2) 6
TOTAL (for eight wkts, 42 overs) 159
FALL OF WKTS: 1-4, 2-19, 3-77, 4-90, 5-90, 6-114, 7-129, 8-150.
BOWLING (to-date): Ntini 13-2-50-1 (2nb, 1w); Terbrugge 4-1-21-2; Hall 4-1-20-0; Adams 13-0-47-2; Kallis 8-2-18-3.—Reuters