win off a maximum of 140 overs.
South Africa's remote hopes of defying history nosedived with the loss of four wickets, including those of skipper Graeme Smith and Hashim Amla, to leave the Proteas battling for survival on Monday's final day.
Australia need to win the three-Test series to take the world number one ranking off South Africa with the final Test starting in Perth on Friday.
At the close of the fourth day, South Africa were 77 for four off 50 overs with AB de Villiers on 12 and debutant Faf du Plessis not out 19.
The odds were already firmly stacked against the South Africans as they needed to set a new record for a successful fourth innings run chase at the Adelaide Oval.
The existing record is the 315-6 Australia scored 110 years ago to overhaul England.
The Australians, bowling with a full head of steam despite the loss of young firebrand paceman James Pattinson, quickly rammed home the advantage of their massive lead.
Australia had South Africa under the pump, taking the wickets of Smith and Amla inside the opening 12 overs to leave the tourists in deep trouble in their daunting run chase.
Smith, who scored 122 in the first innings, was out second ball when he got a thick edge to a Ben Hilfenhaus outswinger and Ricky Ponting snapped up a splendid low catch at second slip.
It was also a psychological blow as the Proteas have not lost a Test match in the previous 25 matches in which talisman Smith has scored a century. Amla was taken at slip by a juggling Clarke off spinner Nathan Lyon for 17, nine balls before tea.
Both Smith and Amla were match-changing scalps for the Australians because of their ability to occupy the crease and bat for long periods.
The wickets continued to tumble with Jacques Rudolph again out cheaply for three, caught at short leg by Ed Cowan off Lyon for the off-spinner's 50th Test wicket.
Alviro Petersen was out seven balls later when he got an inside edge off Peter Siddle onto his stumps for 24 and the Proteas were 45 for four.
De Villiers and du Plessis dug in and it took 30 overs before they claimed their first boundary, when du Plessis edged off Siddle.
Skipper Clarke declared Australia's second innings halfway through the day with Pattinson not out 29 and Hilfenhaus on 18.
Senior Australian batsman Mike Hussey, chasing his third successive century in the series, was out in the over before lunch for 54 off 95 balls. It was his 29th Test half-century.
Hussey attempted to pull Morne Morkel but the ball came off high on his bat to spoon a catch to Dale Steyn at midwicket.
Clarke, who scored 230 in the first innings, fell leg before wicket to Steyn for 38.
Brief Scores: Australia 550 & 267/8 dec (M Hussey 54, M Morkel 3-50) v South Africa 388 & 77/4 in 50 overs (Petersen 24, AB de Villiers batting 12, F du Plessis batting 19)