Enigmatic fly-half Quade Cooper has been handed his first Test start in 12 months while code-hopper Israel Folau will start at full-back as part of a new-look Australia side to face South Africa in Brisbane on Saturday.
Cooper's promotion to the starting XV and Folau's shift from the right wing forces Brumbies young guns Matt Toomua and Jesse Mogg to the bench for the Rugby Championship clash.
Reds loose forward Jake Schatz has been named on the bench and is in line for a possible Test debut, with Liam Gill omitted from the squad alongside Brumbies centre Tevita Kuridrani.
The controversial 25-year-old fell out with former coach Robbie Deans last year and was forced to start from the bench in McKenzie's first two Tests in charge against the All Blacks last month.
"We have very specific thoughts about how we want to play this game and feel Quade is best suited to carrying that out," McKenzie said of Cooper, who has not started a Test since last September against Argentina.
"He's been part of our matchday squad in both games (against New Zealand) so far but his role now changes from being a finisher to starting the game and 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.
"It has been almost 12 months since he last started a Test match and I'm sure there were times where he wondered if he would wear the number 10 jersey again.
"He's worked really hard both on and off the field to now get that chance.
"He's carried himself extremely well all year and during the last fortnight in the role we've asked him to complete, but now he gets a chance to make an impact from the start of the game."
McKenzie added of the decision to shift Folau to full-back and the inclusion of Cummins and Kepu: "Israel has played more full-back than on the wing so he will undoubtedly feel comfortable playing the position.
"He has looked impressive at training and we think he will add value with how we want to approach the game.
"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.
"Up front 'Keps' has been on the fringes but he is a very good technician of the game, which is important as everyone continues to work out the new scrum laws.
"We've got a lot of good players in this space and for this week Keps deserves an opportunity to start."
Australia team to face South Africa: Israel Folau; Nick Cummins, Adam Ashley-Cooper, Christian Lealiifano, James O'Connor; Quade Cooper, Will Genia; James Slipper, Stephen Moore, Sekope Kepu, Rob Simmons, James Horwill (captain), Scott Fardy, Michael Hooper, Ben Mowen.
Replacements Saia Faingaa, Scott Sio, Ben Alexander, Kane Douglas, Jake Schatz, Nic White, Matt Toomua, Jesse Mogg.