Ruan Combrinck and Warren Whiteley have been handed their first starts for South Africa in Saturday's crucial series decider against Ireland in Port Elizabeth.
Ireland upset the odds to earn a historic first win on South African soil in the opening match of the three-Test series despite finishing the game with 14 men, but Joe Schmidt's side squandered a 16-point lead with 20 minutes remaining in Johannesburg in the second contest last weekend.
The tourists can still clinch a first series win in South Africa, but the hosts have brought in Combrinck and Whiteley, who impressed as replacements in the comeback victory, in an attempt to deny the Irish history.
Duane Vermeulen, and Lwazi Mvovo are the men to drop out of the starting XV, the former has an elbow injury while the latter is named among the replacements.
Prop Trevor Nyakane is injured, while uncapped duo Jaco Kriel and Steven Kitshoff are among the reserves.
After falling behind to Ireland last week, South Africa loose-head prop Tendai Mtawarira says the Springboks are targeting an improved start.
"I think we are going to have to start much better than what we did this past weekend," he told rugby365.com.
"We need to make sure that our discipline is really good and we avoid making all those little errors that we made when we got into their 22."
Ireland are feeling the physical effects of their 32-26 defeat last time out, but winger Andrew Trimble insists Joe Schmidt's side are ready to make history.
"It's important that we get some perspective back and just remember that we still have a great opportunity to create history," the winger said.
"We're more aware now than we ever have been with how tough it's going to be, how physical they are, how fast South Africa are.
"We're pretty knackered. It was a tough battle out there, very physical and very fast. In the second half, we were just taking a lot of heat and a lot of punishment."
Tiernan O'Halloran comes into the Ireland side for the injured full-back Jared Payne, while Luke Marshall returns to the starting line-up at outside-centre as Ireland make five changes from the second Test.
Uncapped Matt Healy is named among Ireland's replacements, as is veteran scrum-half Eoin Reddan, who is in line to make his final international appearance after announcing on Thursday that he is quitting rugby to take a job in the aviation finance sector.
South Africa team: Willie le Roux, Ruan Combrinck, Lionel Mapoe, Damian De Allende, JP Pietersen, Elton Jantjies, Faf de Klerk; Tendai Mtawarira, Adriaan Strauss, Frans Malherbe, Eben Etzebeth, Pieter-Steph du Toit, Francois Louw, Siya Kolisi, Warren Whiteley.
Replacements: Bongi Mbonambi, Steven Kitshoff, Julian Redelinghuys, Franco Mostert, Jaco Kriel, Rudy Paige, Morne Steyn, Lwazi Mvovo.
Ireland team: Tiernan O'Halloran, Andrew Trimble, Luke Marshall, Stuart Olding, Keith Earls, Paddy Jackson, Conor Murray; Jack McGrath, Rory Best, Mike Ross, Iain Henderson, Devin Toner, CJ Stander, Jordi Murphy, Jamie Heaslip.
Replacements: Sean Cronin, Finlay Bealham, Tadhg Furlong, Ultan Dillane, Rhys Ruddock, Eoin Reddan, Ian Madigan, Matt Healy.