Clarke backed up his unbeaten double century from last week's drawn Brisbane series-opener with another overpowering innings, becoming the first person in the history of Test cricket to post four 200s in a calendar year.
David Warner and Michael Hussey compounded the misery for the Proteas with quickfire tons as Australia romped to 482 for five on the opening day at Adelaide.
It was just the fifth time in all Tests that Australia have scored more than 400 runs in a day's play.
Unchallengeable Clarke has yet to be dismissed in this series and has amassed 483 runs. He is also this year's highest-scoring Test batsman with 1265 runs at 140.55.
At the close he was unconquered on 224. Hussey was bowled by Dale Steyn in the final over for 103 after raising his 18th century with a six off dispirited legspinner Imran Tahir, who finished the day wicketless for 159 off 21 overs.
"It's always the plan when you get on top to stay on top. When you grab momentum you've got to hang onto it for as long as possible," Clarke said.
"It's a really positive day for the batting group but we've got a lot of work to do over the next four days to have a crack at winning this Test match, that's for sure."
South Africa looked far from the world's best team as their bowlers were hammered, after having the home side in trouble at 55 for three in the morning session.
Warner wrested back control with a belligerent 119 off 112 balls and Clarke and Hussey carried on the run plunder.
It was a thoroughly miserable day for the Proteas with three of their leading bowlers having injury concerns — Vernon Philander withdrawing before the match with a back problem and Jacques Kallis and Dale Steyn leaving the ground during the day with hamstring trouble.
Kallis will not bowl again in the match but will be able to bat, the Australian Associated Press reported.
"The Australian batsmen put us under pressure on a good wicket and created some momentum — some very fast momentum," said Proteas coach Gary Kirsten.
"Sometimes in that situation it's very difficult to pull it back.
"I don't think we bowled well enough throughout the day to really put enough pressure on the batsmen at any time."
Clarke survived a referral on 73 and made the Proteas pay dearly with another commanding knock. He is averaging over 70 with the bat since he became captain last year.
In one Morkel over the sublime Clarke hit five boundaries to raise his 150 and earn a standing ovation from the home crowd.
The home side had seized control with a blistering 178 runs off just 26 overs in the middle session.
Warner was in a punishing mood after lunch, smashing spinners Tahir and Faf du Plessis and racing to his third Test century off 93 balls. He reached his hundred with a six and a four off successive Tahir deliveries.
But Warner perished on 119 when he attempted to glide Morne Morkel through the slips, only to edge to Graeme Smith at first slip. He had crashed four sixes and 16 boundaries, putting on 155 runs with Clarke in 24.2 overs.
It was a rousing fightback by Australia after they lost three wickets in the morning session as South Africa suffered two injuries.
Ed Cowan was caught and bowled for 10 off Kallis's third ball, an attempted yorker which struck him on the boot and spooned up off the bat for a dolly return catch.
Rob Quiney, who kept his place when Shane Watson failed to recover from a calf injury, went for an eight-ball duck when Morkel enticed him to edge to Smith at first slip.
Ricky Ponting's woes continued when he was bowled third ball for just four, playing inside Kallis.
The former Test skipper was out for a five-ball duck in Brisbane for his third duck in four Test innings against the Proteas. He fared little better in Adelaide, stumbling and losing his footing. – AFP