Smith was 111 not out at the close out of a total of 217 for two as the first day batting heroics of home captain Michael Clarke were brought to an abrupt halt.
The Proteas ended the day 333 runs behind and also had the satisfaction of bringing Clarke's impressive innings to an end. Morne Morkel - who claimed five for 146 - was the star in the morning as Australia were bowled out just before lunch for 550, only James Pattinson (42) offering any resistance.
Thereafter it was all about Smith, Alviro Petersen (54) and Jacques Rudolph (25 not out) as South Africa looked to keep a foothold in the Test.
After registering a record fourth double century of the year on a day when Australia scored 482 runs, Clarke would have hoped for more of the same. But it was not to be as, in the fifth over of the day, he was trapped on the crease and bowled by Morkel, who then got Matthew Wade to edge behind moments after Australia had passed 500.
Rory Kleinveldt claimed his first Test wicket as Peter Siddle edged to Smith at first slip, before Morkel got his fifth of the innings when Ben Hilfenhaus top-edged a hook. That meant Australia had slipped to 504 for nine, but Pattinson prolonged the innings as he took a liking to leg-spinner Imran Tahir, whose two overs cost him 21 runs.
Faf du Plessis fluffed an easy chance, but it did not prove too costly as Pattinson edged Dale Steyn two overs later and Smith held a juggling catch at slip.
Pattinson had no success with the ball, though, Smith taking three fours off his third over, two of them clipped through the leg side. When Petersen took two more boundaries off the quick bowler's next over, Clarke turned to the spin of Nathan Lyon, which succeeded in slowing the run-rate, and South Africa edged past 50 just before drinks.
Smith greeted Hilfenhaus' return to the attack by driving him for four, but he should have been dismissed when Clarke brought himself on to bowl and drew a false stroke from his opposite number as he advanced down the pitch. Wade missed the stumping. Smith took advantage to reach 50 just before tea and went on to make a century.
He lost opening partner Petersen when he was run out by Michael Hussey and Hashim Amla was stumped by Wade off David Warner for 11. But with Smith on 111 and Rudolph looking set much will depend on how South Africa start the third day as they look to haul themselves back into the match.