Dean Elgar (23) and Faf du Plessis (26) were the unbeaten batsman at the interval for the hosts as they shared in a 53 run third wicket stand.
Ryan Harris was the pick of the bowlers with 1/10 in seven overs.
In overcast conditions, Australia struck with the new ball.
Captain Graeme Smith and Hashim Amla were both out lbw, as South Africa fell to 11 for two. Smith was out to Ryan Harris, and Amla was removed by Mitchell Johnson.
Earlier, Smith was rushed at the toss as team management made late changes to the team. Smith won the toss and chose to bat.
South Africa made three changes to the side which lost to Australia in the first Test.
Quinton de Kock, Dean Elgar and Wayne Parnell came into the team for Alviro Petersen, Robin Peterson and Ryan McLaren.
The match would be the debut for De Kock, listed to bat at number seven.
South Africa trail Australia 1-0 in the three-match series.