Scrum-half Du Preez missed the 2010 international season because of a shoulder operation while flanker Brussow was sidelined by a knee ligament injury.
The duo are among 13 changes Springboks coach Peter de Villiers has made to his team that lost 40-7 to New Zealand in Wellington on July 30, with captain John Smit and loose forward Danie Rossouw the only survivors.
The selection also marks the return for the first time in a year of another four players - JP Pietersen, Jaque Fourie, Butch James and Gurthro Steenkamp.
"We still have a number of leading players unavailable through injury but this is the strongest squad we have been able to choose from since 2009," said De Villiers.
"It's great to have Fourie and Heinrich back as they were two of the leading players in world rugby when they last played in 2009, and they contributed a lot to Springbok success that season.
"This is the first step back for them, but we're looking to them to have the same impact in due course."
The starting XV is the most experienced in the history of Springbok rugby with a combined total of 810 caps.
De Villiers added: "This team has vast experience and a strong leadership core, but that counts for nothing at kick off on Saturday.
"This Australian team are no respecter of reputations - we saw that last year in Bloemfontein - and we know just how dangerous they can be.
"They will be highly motivated and hurting after their last result and they have a good recent record against us. They will know we have just come together and they'll be looking to exploit that."
South Africa team: F Steyn; JP Petersen, J Fourie, J de Villiers, B Habana; B James, F du Preez; T Mtawarira, J Smit (capt), J du Plessis, B Botha, V Matfield, H Brussow, D Rossouw, P Spies.
Replacements: B du Plessis, G Steenkamp, G Mostert, J Deysel, F Hougaard, M Steyn, G Aplon.
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