The Australia captain became the first man in Test history to score four double centuries in a calendar year, hitting 39 fours and a six to finish the day on an 224 in Adelaide.
Dale Steyn, the world's top-ranked test bowler, took himself off after tea with another suspected hamstring strain,
Opener David Warner (119) and veteran Michael Hussey (103) also compiling centuries and hitting four sixes apiece.
But when Clarke arrived at the crease South Africa, who had lost the toss, were well in the game having struck early to leave the home side on 55 for three.
But while there were failures for Ed Cowan, Rob Quiney and Ricky Ponting, Warner and Clarke and Hussey led the fightback superbly.
Steyn, having returned to the field, finally broke the 272-run partnership when he bowled Hussey with the last ball of the day - but it was scant consolation for the Proteas.
South Africa's bowlers ended with ugly figures, with Tahir going wicketless for 159 runs, pillaged for more than seven runs an over.
The tourists face a Herculean task to turn things around at Adelaide and could lose their top test ranking should they lose the three-match series.
Listen to Michael Clarke and David Warner talk about the opening day performance and the pitch on our player below:
Follow us @SprtNationalUAE