Fava's inclusion is one of four changes Wallabies coach John Connolly has made to his first XV as they look to bounce back from the defeat in Christchurch.
Matt Giteau, who also impressed from the bench in the All Blacks match following his return from injury, will start at inside centre while hooker Jeremy Paul and back-rower Rocky Elsom have both been drafted into the forwards.
"I thought Mat Rogers had played extremely well during the first four Tests and is very unlucky to miss out, but we want to see what Giteau can bring to the team at inside centre," Connolly said.
"The back row was another difficult call but I thought Scott Fava deserved the opportunity to start after his performance against New Zealand and Rocky Elsom returns to blindside flanker where he has played the majority of his Test rugby."
Australia also welcome back winger Clyde Rathbone following a hamstring injury and he takes his place on the bench, alongside hooker Sean Hardman, who has been named in the 22 for the first time since making his Test debut against France in 2002.
Saturday's clash between Australia and South Africa will be the first of a three-match series for the Mandela Plate, as well as being the second match of the Tri-Nations series.
South Africa currently hold the Mandela Plate after winning a one-off Test at Ellis Park last year.
Australia: Chris Latham; Mark Gerrard, Stirling Mortlock, Matt Giteau, Lote Tuqiri; Stephen Larkham, George Gregan (captain); Greg Holmes, Jeremy Paul, Guy Shepherdson, Nathan Sharpe, Dan Vickerman, Rocky Elsom, George Smith, Scott Fava.
Replacements: Sean Hardman, Al Baxter, Mark Chisholm, Phil Waugh, Sam Cordingley, Mat Rogers, Clyde Rathbone.