South Africa have brought in Adriaan Strauss and Fourie du Preez for Bismarck du Plessis and Ruan Pienaar to face Australia.
Jannie du Plessis and Morné Steyn will reach the special milestone of playing in their 50th Tests for South Africa against Australia at Newlands in Cape Town on Saturday, as Adriaan Strauss and Fourie du Preez have been promoted to the Springbok starting line-up.
It will be the second time in Springbok history that two players will earn their 50th caps in the same Test - on 1 August 2009 Jean de Villiers and Bryan Habana, now the two most experienced members of the squad, reached this special milestone together against New Zealand in Durban.
Du Plessis and Steyn will become the 25th and 26th Springboks to play in 50 Tests for South Africa. Steyn also needs two points to move to 600 Test points for the Boks - he is currently on 598 in his 49 Tests to date.
The last Springbok to play in his 50th Test was Jannie's brother Bismarck du Plessis, against Argentina in Mendoza last month, which means they will become the first set of brothers ever to play in 50 Tests for South Africa.
Du Preez will start his first Test for the Springboks since the 2011 Rugby World Cup quarter-final against Australia in New Zealand.
The rest of the team that played against New Zealand in Auckland is unchanged.
"We're all very pleased for Jannie and Morné, who are great ambassadors for South Africa and the Springboks," said Springbok coach Heyneke Meyer.
"They have endured through difficult times but have shown a lot of resilience and that is why they have made it to this special milestone. It's well-deserved and a privilege only a very small percentage of Springboks have achieved.
"The players all knew what the plans were for the Rugby Championships and where they stand. We were always going to rotate players where possible and planned to start this Test with Adriaan and Fourie.
"We know we're in for a big challenge against Australia. The players have been working very hard and we're looking forward to playing in front of our own supporters at Newlands on Saturday - it's always special to play Tests in South Africa."
South Africa: 15 Zane Kirchner, 14 Willie le Roux, 13 JJ Engelbrecht, 12 Jean de Villiers (captain), 11 Bryan Habana, 10 Morné Steyn, 9 Fourie du Preez, 8 Duane Vermeulen, 7 Willem Alberts, 6 Francois Louw, 5 Flip van der Merwe, 4 Eben Etzebeth, 3 Jannie du Plessis, 2 Adriaan Strauss, 1 Tendai Mtawarira.
Replacements: 16 Bismarck du Plessis, 17 Gurthrö Steenkamp, 18 Coenie Oosthuizen, 19 Juandré Kruger, 20 Siya Kolisi, 21 Ruan Pienaar 22 Pat Lambie, 23 Jan Serfontein.
Date: September 28
Venue: Newland Stadium, Cape Town
Kick-off: 17:00 (16:00 GMT)
Referee: Jérôme Garcès (France)
Assistant referees: Nigel Owens (Wales), Pascal Gauzère (France)
Television match official: Graham Hughes (England)