Since returning to international cricket in 1991, South Africa have beaten every other Test nation except Australia in home and away series.
Smith has twice led South Africa to triumphs in Australia but a home series win has eluded Smith and his predecessors. In six previous tours by Australia going back to 1993/94 the visitors have been victors four times with two series shared.
It seemed the sequence would continue when a Mitchell Johnson-inspired Australia won the first Test of the current series by 281 runs at Centurion - but world champions South Africa bounced back in emphatic style with a 231-run win in Port Elizabeth last weekend.
Now the hosts have an opportunity to clinch the series at a ground which has been a fortress for South Africa, who have won 18 of 26 post-isolation Tests at Newlands, with only three defeats - all against Australia.
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South Africa are expected to make two significant changes to their team. Opening batsman Alviro Petersen, who withdrew from the second Test because of illness, is set to return despite his replacement Dean Elgar playing a crucial innings of 83 in Port Elizabeth. Elgar is likely to drop down the order to number six or seven.
With left-arm fast-medium bowler Wayne Parnell ruled out with a groin injury, South Africa have to decide whether to pick all-rounder Ryan McLaren, who suffered concussion when struck by a bouncer from Johnson in Centurion, or a specialist bowler.