The Springboks must win at Newlands in Cape Town to have a realistic chance of bridging a four-point gap behind leaders New Zealand and topping the final standings.
And coach Heyneke Meyer says Japan-based Du Preez can play a key role in his first green-and-gold start since the 2011 Rugby World Cup in New Zealand.
Many pundits believed the then 30-year-old was past his prime after quitting the Bulls last year for a Suntory Sungoliath outfit coached by Australian Eddie Jones.
But Meyer begs to differ, believing Du Preez could be his first-choice No 9 come the 2015 Rugby World Cup in England.
"Watching Fourie train this week you realise what a great player he is," said former Bulls boss and Super Rugby-winning coach Meyer.
"Without taking anything away from Ruan Pienaar, who has also been good and is very experienced, Fourie is in a class of his own.
"The main thing about him is that we have an extra coach on the field. He is calm, organises the defence, the attack, and the kicking game.
"His presence takes pressure off (skipper) Jean de Villiers," Meyer said ahead of the return match with the Wallabies, who suffered a humiliating 38-12 drubbing n Brisbane this month.
"Fourie has the ability to find players in space, or put them into space. He is a magnificent player with great organisational skills."
Flyhalf and star goal-kicker Morne Steyn is thrilled at renewing a half-back partnership that laid the foundations for many Springboks victories.
"Fourie brings something extra that no other scrumhalf can. The way he reads and controls the game makes such a difference to the flyhalf," said Steyn.
"He takes a lot of pressure off me," added the leading points scorer with 68 in the 2013 southern hemisphere championship.
Du Preez for Pienaar is one of two starting-team changes made by Meyer after a controversial 29-15 away loss to greatest rivals New Zealand this month.
Hooker Bismarck du Plessis was unfairly sin-binned in the first half and when he got a justifiable second yellow card soon after half-time, was sent off.
The Springboks host the All Blacks next weekend, but the match will lose considerable appeal if South Africa lose in Cape Town and New Zealand win in Argentina.
Du Plessis drops to the bench for Newlands with Adriaan Strauss starting, although Meyer stressed that the decision was part of a rotation plan.
Strauss expects the Wallabies, who suffered four straight Test losses before edging Argentina two weeks ago, will be much tougher to beat than in Brisbane.
"That defeat would have stung them and they will be supremely motivated. They will be looking to up their game, especially the forwards.
"But we are also positive and have been working hard on our scrumming - an area that has gone well for us this season."
Australia seek to end a five-match losing streak in Cape Town with a team showing three changes from that which began against the Pumas in Perth.
Centre Tevita Kuridrani, left-wing Joe Tomane and lock and skipper James Horwill are called up at the expense of suspended James O'Connor, injured Nick Cummins and axed Kane Douglas.
There is also a positional switch with Adam Ashley-Cooper moving from outside centre to the right wing to accommodate Kuridrani.
Coach Ewen McKenzie replaced New Zealander Robbie Deans after a mid-year 2-1 series loss to the touring British and Irish Lions.
But the former Wallaby prop is upbeat despite three losses in his four outings, insisting the squad are not out of their depth.
"It is not like the Springboks were way out of our league. We did not get to the game plan we wanted last time so we have stuff up our sleeve.
"You need to fight fire with fire to some extent against South Africa and it is pretty clear that we have brought in extra bulk."
McKenzie was part of the last Australian side to savour success in Cape Town - winning 26-3 at Newlands 21 years ago.
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
Substitutes: 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
15 Israel Folau, 14 Adam Ashley-Cooper, 13 Tevita Kuridrani, 12 Christian Leali'ifano, 11 Joe Tomane, 10 Quade Cooper, 9 Nic White, 8 Ben Mowen, 7 Michael Hooper, 6 Scott Fardy, 5 James Horwill (captain), 4 Rob Simmons, 3 Ben Alexander, 2 Stephen Moore, 1 James Slipper
Substitutes: 16 Saia Fainga'a, 17 Benn Robinson, 18 Sekope Kepu, 19 Sitaleki Timani, 20 Ben McCalman, 21 Will Genia, 22 Matt Toomua, 23 Chris Feauai-Sautia