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Pocock was named to start at No.8 but has struggled to overcome the injury after failing a last-minute fitness test before Friday's captain's run in Brisbane.
He has been replaced by Pete Samu, who comes from outside the 23-man squad and will now join captain Michael Hooper and Lukhan Tui in the back row for his maiden test start.
Samu's five appearances for the Wallabies have all come off the bench.
Losing Pocock is a major blow for Australia, who, like the Springboks, desperately need a win to restore some pride with both teams coming off disappointing losses.
It's expected Israel Folau will take his place in the line-up at Suncorp Stadium after participating in Friday's session and showing no sign of discomfort in his ankle.
Folau had missed the second Bledisloe Cup test with injury.
Wallabies: Israel Folau, Dane Haylett-Petty, Reece Hodge, Matt Toomua, Marika Koroibete, Kurtley Beale, Will Genia, Pete Samu, Michael Hooper (capt), Lukhan Tui, Adam Coleman, Rory Arnold, Allan Alaalatoa, Tatafu Polota-Nau, Scott Sio. Res: Folau Faingaa, Tom Robertson, Taniela Tupou, Izack Rodda, Ned Hanigan, Joe Powell, Bernard Foley, Jack Maddocks.