Wallaby fly-half Quade Cooper has been recalled to the starting XV while Israel Folau moves to full-back for Saturday's Test with the Springboks in Brisbane.
Australia have lost both their opening matches in the Rugby Championship to New Zealand, forcing new coach Ewen McKenzie to shuffle the back-line for the crucial Brisbane showdown.
The addition of Cooper and the shift from the wing for Folau represent two of four changes to the run-on side, which also include Sekope Kepu and Nick Cummins getting an opportunity at tighthead prop and on the wing.
Cooper fell out of favour under former Australia coach Robbie Deans and Saturday will be the first time he has has worn the number 10 jersey since the Wallabies defeated South Africa and Argentina in back-to-back Tests in September last year.
He is now well and truly in the mix under his former Reds mentor McKenzie, who said Cooper, reunited with scrum-half and Reds team-mate Will Genia, deserved to be back.
"We have very specific thoughts about how we want to play this game and feel Quade is best suited to carrying that out," he said.
"He's been part of our matchday squad in both games so far but his role now changes from being a finisher to starting the game. We feel that role will suit how we want to play.
"He is also an experienced and successful Test player, which is handy to have against a hardened Springboks outfit."
Folau, who rebuffed a return to the National Rugby League by signing a two-year deal with the Australian Rugby Union last week, has played all of his five Tests so far on the wing.
But McKenzie now sees his attacking potential best used at full-back.
"Israel has played more fullback than on the wing so he will undoubtedly feel comfortable playing the position," he said.
"He has looked impressive at training and we think he will add value with how we want to approach the game."
His move opens the door for Western Force winger Cummins, who has been given his first opportunity of 2013, adding to the six Test caps he has earned since making his debut against Argentina last year.
"Once we made the decision to move Israel it opened the door for another player on the wing. The Springboks are an abrasive and physical team and we feel Nick's style of play will suit that," said McKenzie.
On the bench, Reds backrower Jake Schatz is in line to make his long-awaited Test debut.
The Springboks, coming off back-to-back wins over Argentina, have never won in eight Tests in the Queensland state capital, including seven since the inception of the Tri Nations/Rugby Championship in 1996.
Australia: 15 Israel Folau, 14 Nick Cummins, 13 Adam-Ashley Cooper, 12 Christian Lealiifano, 11 James O'Connor, 10 Quade Cooper, 9 Will Genia, 8 Ben Mowen, 7 Michael Hooper, 6 Scott Fardy, 5 James Horwill (captain), 4 Rob Simmons, 3 Sekope Kepu, 2 Stephen Moore, 1 James Slipper.
Replacements: 16 Saia Faingaa, 17 Scott Sio, 18 Ben Alexander, 19 Kane Douglas, 20 Jake Schatz, 21 Nic White, 22 Matt Toomua, 23 Jesse Mogg.
Date: September 7
Venue: Suncorp Stadium, Brisbane
Kick-off: 20:05 (10:05 GMT)
Referee: George Clancy (Ireland)
Assistant referees: Nigel Owens (Wales), Glen Jackson (New Zealand)
Television match official: Ben Skeen (New Zealand)
Assessor: Clayton Thomas