South Africa were 127 for four at lunch in reply to Australia's 494 for seven declared.
South African captain Graeme Smith failed again when he was caught behind off Ryan Harris for five in the fifth over. Smith has made only 42 runs in five innings in the series.
Dean Elgar made 11 before he was superbly caught by wicketkeeper Brad Haddin off James Pattinson.
At that stage South Africa were 42 for two. Alviro Petersen and Hashim Amla added 53 off 58 balls with Petersen reaching a fluent half-century off 50 balls with eight fours.
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Amla looked in good form, but was bowled for 38 when Harris made a ball swing back sharply to find a gap between bat and pad.
Harris was the most impressive of the Australian bowlers, taking two for 18 off nine overs.
With play starting 30 minutes earlier because of rain which cut 51 overs from the second day's play, Clarke declared overnight.
It proved a shrewd move because there was early movement off the pitch for the bowlers, with Smith caught off a ball from Harris which seamed away from him.