Ed Cowan's maiden international century and an unbeaten double ton from captain Michael Clarke ensured that any hopes South Africa had of forcing a result in the first Test were all but wiped out at the Gabba after the hosts finished day four on 487 for four.
Chasing the Proteas' first innings effort of 450, Cowan hit 136 in a partnership of 259 with his skipper, before finally suffering an unfortunate run out to be the only the wicket of the day in Brisbane.
Clarke, who plundered 150 against the same opposition in Cape Town last year, finished the day on 218 with Michael Hussey (86no) picking up where Cowan left off.
With day two lost to rain Australia made steady accumulation the order of the day.
In two and a half hours of cricket before lunch they scored 103 runs with barely a scare and such was the unthreatening nature of the South Africa attack that Graeme Smith, who is without a frontline spinner in this game, chose to bowl himself.
Cowan got the single he needed to reach 50 in the first over, and Clarke followed him with a square drive off Test debutant Rory Kleinveldt shortly after bringing up the 100 partnership.
Progress was slow, Australia going more 16 overs without finding the boundary at one point, before Cowan pulled Smith, without a Test wicket since 2005, for four.
Cowan was given a hand when he was credited with a four which took him to 98 in the penultimate over before lunch when the ball actually came off his helmet.
By lunch, the partnership, which began with Australia in real danger on 40 for three, had reached 174.
Cowan pulled Vernon Philander for four in the second over after the resumption and that briefly seemed to free both batsmen, Clarke taking three fours off the next Morne Morkel over to move into the 90s.
Clarke took a single to bring up the 200 stand, then crept towards 100 before finally reaching the milestone in similar fashion.
A mix-up between Dale Steyn and Jacques Rudolph in the deep saw Cowan dropped on 123, but Steyn made up for his part in the error when he got a finger to the ball to run the same batsman out backing up just before tea.
By the break Australia were 144 behind the tourists' total.
South Africa's frustration was summed up in two events after tea.
First they wasted a review on a caught-behind appeal, when replays showed the delivery from Philander had been nowhere near Clarke's bat.
Then Clarke got an inside edge through to wicketkeeper AB de Villiers from a Morkel no-ball.
Clarke was scoring more freely by that point and he took advantage of his let-off, reaching 150 with a clip into the leg side for two.
While at the other end Michael Hussey helped himself to a 68-ball half century, pushing the home side to 400 for four.
Smith brought Hashim Amla into the attack in an attempt to prize either batsman out.
However, he failed to test the concentration of the pair as they pushed the Australians past the South African's first innings total as Clarke hit two consecutive boundaries off Morkel in the 114th over.
Two overs later and Clarke reached his third double century of 2012 with an immaculately timed on drive boundary off Steyn.