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.
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.
Proteas batter Marques Ackerman admits he "left a Test hundred out there" after falling for 95 on the opening day of the third and deciding Test against Australia at Newlands on Tuesday.
The Proteas got off to a fabulous start in the third and deciding Test against Australia at Newlands, but the tourists hit back in the final two sessions as the home side were 329 all out.
Proteas captain Temba Bavuma admits leaving spinner Keshav Maharaj out of the staring line-up in the last two Test matches against Australia has been "one of the tougher decisions to be a part of".
