Ndungane missed the 35-17 loss to New Zealand because of a shoulder injury and will win his second cap while Muller replaces his Sharks team-mate Albert van der Berg in the second row for his third appearance in the national side.
On the bench, South Africa Under-21 captain Mahlatse 'Chiliboy' Ralepele is in line to make his Test debut.
Ralepele has already led his country's U19 and U21 teams to success and is widely tipped to become the first black captain of the Springboks in the next few years.
Having just turned 20, the Blue Bulls hooker was captain when South Africa won the IRB U19 World Championship in 2005 and also played in the side that won the IRB U21 World Championship later in the same year.
This year he was skipper of the U21 side that was pipped by host nation France in the IRB U21 Championship final.
Ralepele has played just eight minutes of Super 14 rugby but on Saturday he may be called upon to replace Springbok captain John Smit at some point in the game.
Smit will win his 36th consecutive cap as captain when he runs onto the field against the Wallabies while fullback Percy Montgomery is just two away from reaching 100 conversions in Test rugby.
If he does that this weekend he will also equal Piet Visagie's record of 11 career conversions against Australia, a record that has stood since 1971.
South Africa team: Percy Montgomery; Akona Ndungane, Jaque Fourie, Wynand Olivier, Bryan Habana; Butch James, Fourie du Preez; Os du Randt, John Smit (captain), CJ van der Linde, Johann Muller, Victor Matfield, Solly Tyibilika, Juan Smith, Jacques Cronje.
Replacements: Chiliboy Ralepele, Eddie Andrews, Albert van der Berg, Joe van Niekerk, Ricky Januarie, Meyer Bosman, Jaco van der Westhuyzen.