The disastrous record of the Springboks there began in 1997 when beaten 32-20 by the Wallabies and includes a humiliating 49-0 drubbing nine years later.
South Africa coach Rassie Erasmus is aware of the jinx, saying "Australia are a quality team and, historically, a force to be reckoned with at home".
The Springboks leave Johannesburg on Wednesday for Sydney with a squad lacking some regular first choices due to injuries and a suspension, but containing 22 Rugby World Cup winners.
AFP Sport looks at some of the selection choices facing Erasmus as South Africa seek to emulate the team of 2013, who triumphed by 26 points in Brisbane for the lone Springboks success there.
Fly-half
Handre Pollard, Manie Libbok and exciting new kid on the block Sacha Feinberg-Mngomezulu are the contenders for the No. 10 shirt.
Pollard boasts experience and eight successes from eight kicks at goal in a last-gasp one-point loss to Ireland this month emphasised his strength, but he is less impressive with ball in hand.
Libbok is a more creative playmaker, but an erratic goal kicker, while 22-year-old Feinberg-Mngomezulu has consistently impressed in four appearances off the bench.
Scrum-half
With first choice Faf de Klerk recovering from an undisclosed injury, Cobus Reinach, Grant Williams and Morne van den Berg are vying to start.
Unlike De Klerk, whose reputation has been built largely on a kicking game, the three contenders for Brisbane love to run with the ball when feasible.
With Van den Berg having just one cap, off the bench in a recent 10-try romp against Portugal, South Africa are likely to start with Reinach or Williams.
Eighthman
Erasmus chose 33 players for the trip to Australia, including six loose forwards, but there was no specialist eighthman in the squad.
The popular view is that the head coach will retain Kwagga Smith, who started in both matches of a drawn home series with Ireland, or Elrigh Louw, who came off the bench against Portugal.
Powerful ball-carrier Louw can be deployed as a line-out option and is good under the high ball -- factors which could give him the edge.
Bench
Erasmus favours versatility and Feinberg-Mngomezulu (fly-half, centre, full-back) and Williams (scrum-half, wing) cover all seven backline positions.
If he picks the pair as replacements, he is likely to go with a six forwards-two backs split on the bench.
Props Gerhard Steenekamp and Vincent Koch, lock Salmaan Moerat, who captained South Africa against Portugal in only his seventh Test, and flanker Ben-Jason Dixon are likely choices.
Championship strugglers
While South Africa have won the Rugby World Cup a record four times -- once more than greatest rivals New Zealand -- they have only one Rugby Championship title to boast of.
New Zealand have dominated the four-nation southern hemisphere tournament since its launch in 2012, topping the final standings nine times.
Australia and South Africa have been champions once each and the 2020 edition had only three teams, including Argentina, because the Covid-19 pandemic prevented the Springboks taking part.
