A string of injuries to key personnel has forced Springbok coach Jacques Nienaber to ring the changes following his side's recent loss to the Wallabies on Saturday.
New faces have been brought into the squad, while there have been several rotations to the side that lost 25-17 in Adelaide.
The 5-3 forwards-backs bench split has been retained.
Handre Pollard, Lukhanyo Am and Pieter-Steph du Toit were all ruled out due to knee injuries, while Elton Jantjies injured his hand and was not available for selection this weekend.
Steven Kitshoff will start at loosehead prop alongside hooker Malcolm Marx and tighthead prop Frans Marlherbe.
Nienaber has also reshuffled his loose trio with captain Siya Kolisi partnering Franco Mostert and Jasper Wiese.
The Bok backline will also see several changes this weekend as Jaden Hendrikse starts at No 9, Damian Willemse will do duty at 10 and Jesse Kriel at outside centre.
Nineteen-year-old Canan Moodie is in line to make his Test debut and will become the fourth player to occupy the position since the start of the Rugby Championship.
More changes have been made to the bench as Deon Fourie, Trevor Nyakane and Cobus Reinach all come in to join Ox Nche, Duane Vermeulen, Kwagga Smith, Frans Steyn and Warrick Gelant.
Saturday's Test in Sydney 11:35 (SA time) on Saturday.
15 Willie le Roux, 14 Canan Moodie, 13 Jesse Kriel, 12 Damian de Allende, 11 Makazole Mapimpi, 10 Damian Willemse, 9 Jaden Hendrikse, 8 Jaspe Wiese, 7 Franco Mostert, 6 Siya Kolisi (captain), 5 Lood de Jager, 4 Eben Etzebeth, 3 Frans Malherbe, 2 Malcolm Marx, 1 Steven Kitshoff
Substitutes: 16 Deon Fourie, 17 Ox Nche, 18 Trevor Nyakane, 19 Kwagga Smith, 20 Duane Vermeulen, 21 Cobus Reinach, 22 Frans Steyn, 23 Warrick Gelant
"We selected a team we thought would be best for this match given that we have several players out with injuries and with an eye on how we want to play," said Nienaber.
"Handre, Lukhanyo, Elton and Pieter-Steph are all carrying injuries which adds to a list that includes Cheslin Kolbe and Sbu Nkosi, while Kurt-Lee Arendse is also out serving a suspension, and this has forced our hand to make a few changes in some positions.
"This will also be a great test for Canan, who was a stand-out player for the Bulls this season in the United Rugby Championship. He’s a very talented player, who will enjoy this opportunity."
Zoning in on the match itself, Nienaber said: "We had a thorough review of our performance against Australia last week, and the most disappointing aspect is that were dominant in several areas of the game, but we struggled to show that on the scoreboard.
"This week is a final for us to stay in the competition and we are expecting Australia to be just as desperate, but so are we."We let ourselves down in the last two games and we are determined to rectify that this week and change our fortunes in Australia. We’ll prepare as well as possible this week to stay in the hunt for the title," he added.