South Africa, who won the toss and chose to bat, were 66 for four at lunch on the first day.
Fast bowler Clark took three for 13 from six overs.
The match started under heavy cloud cover, and there was evidence of assistance for the seam bowlers.
However, runs flowed fairly freely for South Africa's opening pair of Graeme Smith and AB de Villiers.
But in the 10th over fast bowler Michael Kasprowicz moved a delivery off the seam back into the right-handed De Villiers, who drove down the wrong line and was cleanbowled through the gate for eight.
Two balls later Smith survived a confident appeal for leg before off Kasprowicz.
Clark struck first when he angled a delivery across the left-handed Smith, who pushed forward tentatively and edged a catch to wicketkeeper Adam Gilchrist to be dismissed for 19.
Jacques Kallis, who scored six, became Clark's second victim when he cut at a short delivery and was caught by Matthew Hayden in the gully.
Nine balls before lunch Herschelle Gibbs drove down the wrong line to Clark and was bowled for 18 as South Africa stumbled to 61 for four.
Ashwell Prince was four not out at lunch with Jacques Rudolph on one.
South African all rounder Shaun Pollock was forced out of the match by the buttock spasm he suffered during the one-day series.
Pollock was replaced by all rounder Andrew Hall.
Shane Warne was the only spinner named by Australia, who decided to select Clark as a third seamer instead of Stuart MacGill as a second slow bowler.