The Australia captain became the first batsman to score four double centuries in a calendar year when he took a single off Imran Tahir late on the first day at the Adelaide Oval. His 200 came off 226 balls and featured 35 boundaries and a six.
He was unbeaten on 224 when Mike Hussey (103) chopped a Dale Steyn delivery onto his stumps to end their 272-run fifth-wicket stand on the last ball of the day.
Australia produced its highest first-day total in a test match since the 496 scored against South Africa in 1910.
David Warner belted 119 from 112 balls on a day dominated by the batsmen apart from a stumble in the first session when the Australians lost three wickets for 12 runs and slipped to 55-3.
The momentum swung wildly back to Australia after 37-year-old allrounder Jacques Kallis limped off the field in the 17th with an injured right hamstring after dismissing Ed Cowan (10) and Ricky Ponting (4) in his opening 3.3-over spell. He didn't went for MRI scans and didn't return to the field, compounding the pressure on the South African attacked after Vernon Philander was ruled out just hours before the match started with a bad back.
Kallis had 2-19 and Morne Morkel's figures blew out to 2-128 after he was forced to shoulder a heavier workload with Kallis out and Steyn hampered by a tight left hamstring in the evening session.
Warner plundered South Africa's depleted bowling from the start, clobbering four sixes and 16 boundaries in his third test century.
He put on 155 for the fourth wicket with Clarke.
The burly opener smashed Faf du Plessis' first ball in test cricket, a high full toss, over the square leg boundary and lost it in the construction zone to move to 83.
He then hit a six and a four on consecutive balls from legspinner Imran Tahir to reach his 100 from 93 balls, lacing his third test century with 13 boundaries and four sixes before he fended a good length ball from Morkel to Graeme Smith at slip.
Hussey joined Clarke and kept up the momentum, smashing a six against Tahir to bring up his century just one ball after Clarke had reached his 200.