"It's naturally disappointing for the two guys who missed out on the starting team in Nic and Kurtley, but the reality is we have a lot of good players in those playmaking positions."
In the only other starting change, Queensland rake James Hanson has been called up after a season-ending injury to Nathan Charles put further strains on Australia's hooker woes.
To combat the abrasive Springboks pack, McKenzie has opted for a forward-heavy 6-2 split on the bench.
Lock James Horwill returns to the matchday line-up at the expense of behemoth youngster Will Skelton, while Western Force captain Matt Hodgson and Reds hooker Saia Fainga'a get their first opportunities for Australia in 2014.
"Traditionally they [South Africa] are a forward-orientated side which uses their size, power and set-piece to put pressure on the opposition," he said.
"You have to confront that head-on and match fire with fire. The addition of an extra forward also offers us greater flexibility in how we approach our substitutions."
The Wallabies are in last place two rounds into the Rugby Championship. While they drew 12-all in game one against the All Blacks, Argentina has two losing bonus points against South Africa and sits in third place.
Wallabies: Israel Folau, Adam Ashley-Cooper, Tevita Kuridrani, Matt Toomua, Rob Horne, Bernard Foley, Nick Phipps, Wycliff Palu, Michael Hooper (c), Scott Fardy, Rob Simmons, Sam Carter, Sekope Kepu, James Hanson, James Slipper. Res: Saia Fainga'a, Pek Cowan, Ben Alexander, James Horwill, Scott Higginbotham, Matt Hodgson, Nic White, Kurtley Beale.