Having bowled the hosts out for 329 on the stroke of close of play on the opening day, Matt Renshaw and Travis Head gave Australia a decent start with a 58-run stand before spinner Simon Harmer made the breakthrough with the wicket of Head for 41.
The Proteas slow-bowler the got his second dismissal inthe over when Marnus Labuschagne, under pressure to keep his place in the Australia team, was caught at slip for a five-ball duck as the visitors were 58-2.
Renshaw and Cameron Green then halted the momentum that home team had gained with a 126-run partnership for the third wicket as Australia looked to take complete control of the contest.
The Proteas though hit back again with a double strike, left-arm fast bowler Marco Jansen removing both set batters, first having Renshaw caught behind for 74 and then Green edged to slip with the safe hands of Harmer pouncing the catch as the number 4 walked for 65.
At 185-4 the Proteas would have been confident they could restrict the tourists to somewhere in the region of 280-300 but Alex Carey and Josh Inglis had other ideas.
The Aussie duo completely nullified the South African bowling attack and put together an unbroken stand of 145 runs, making Australia take the lead in the final over of the day.
The Proteas will need a big first session on the third day, with quick wickets of they are halt Australia's charge of taking control of the game and perhaps the series.
The Proteas blew Australia's batting order away on the fifth day of the deciding Test at Newlands, the visitors crumbling to 111 all out as the hosts wrapped up a 176-run victory and a 2-1 series win.
South Africa finished day three of the decisive third Test against Australia at Newlands with a narrow 40-run lead after a battling second-innings effort kept the hosts in the contest.
Steve Smith is expected to recover in time for Australia's opening Test against New Zealand in December after medical examinations ruled out significant damage to his neck.
Marco Jansen has attained the number one position in the bowlers' and all-rounders' world rankings after playing a stellar role in the Proteas' innings and 31 runs victory over Australia in the second Test.
