The Proteas have won three successive series in Australia but are 1-0 down going into the traditional Melbourne blockbuster after being crushed by six wickets inside two days in the first Test at the Gabba.
Australia's last Test triumph over South Africa at home came under Ricky Ponting's captaincy during the 2005-06 summer.
A breakthrough series win over the Proteas would set Australia up nicely for a mammoth 2023 when they head to India in February for a four-Test series before trying to retain the Ashes in England.
"Going into next year we've got Indian conditions, Ashes, maybe World Test Championship final - for a Test cricketer it's probably the biggest year you could possibly have," captain Pat Cummins said.
"We've got an opportunity ahead of us to set a legacy for this team and it's so exciting."
Cummins is confident the second Test will last longer than the opening match, when 34 wickets tumbled during just six sessions of play.
Last year's MCG Test finished before lunch on the third day but conditions are not expected to suit fast-bowling as much this time around.
Scott Boland has retained his spot, with fellow quick Josh Hazlewood ruling himself out as he continues to recover from a side strain injury.
The Victorian fast bowler will return to the scene of his famous Test debut last December, when he ran through England with 6-7 to secure man-of-the-match honours and help Australia retain the Ashes.
Boland has taken 25 wickets in his five Tests at the miserly average of 10.36, coming back into the XI when Hazlewood hurt himself in the opening Test of the summer against West Indies in Perth.
Veteran opener David Warner will become just the 14th Australian to play 100 Tests when he lines up against the Proteas, but is facing a fight to bow out of red-ball cricket on his own terms after not making a century in the format since January 2020.
The Boxing Day Test, always a memorable occasion, will be even more special this year as Cricket Australia pay tribute to legendary spin king Shane Warne.
Among other tributes, players from both sides will all wear floppy hats during the national anthems in tribute to the cricket icon, who died suddenly in March.
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