The fiery paceman, who took seven wickets in the first innings, dismissed Alviro Petersen (one) with his fifth ball of the day and added the prize wicket of rival captain Graeme Smith (four) as South Africa slumped to 12 for two in the first session on the fourth day.
The home side lost a third wicket 15 minutes before lunch when Faf du Plessis (18) was trapped leg before by a Peter Siddle delivery that kept low.
South Africa were 65 for three at lunch with Hashim Amla (22) and AB de Villiers (four) in the middle.
Fresh from his man-of-the-series performance in the Ashes whitewash of England, Johnson looked almost unplayable in the first innings as his raw pace and the disconcerting bounce he generated saw South Africa bowled out for 206, 191 runs behind Australia's first innings tally of 397.
On Saturday, he had Petersen edging to wicketkeeper Brad Haddin to claim his 250th test wicket and then hit Amla in the grill of his helmet with the next ball, a rising delivery that forced the batsman onto the back foot but kept creeping up towards his face. Amla was unhurt.
Smith was snapped up at short leg by Alex Doolan, playing a round the corner shot, in a major blow to the slim home hopes of salvaging the test.
Earlier, Australia captain Michael Clarke made a quick decision to declare after just 3.2 overs on day four, seeing enough zip in the wicket after he and Shaun Marsh survived some hostile bowling.
Two extras were added to the overnight total of 288 for three before Marsh was caught behind by De Villiers off Dale Steyn and Clarke immediately declared, his side enjoying a mammoth lead and with ample time to bowl South Africa out for victory in the first of the three-test series.
(Editing by Amlan Chakraborty)
