Loosehead prop Benn Robinson makes his Test debut while Australia Sevens star Cameron Shepherd comes in on the wing for his first start in a Wallaby jersey.
Robinson, at 22 the youngest member of the Wallabies squad, will be the seventh debutant used by Connolly in nine Tests this season.
Shepherd, who played in the opening three Tests of the season from the bench, comes in for Lote Tuqiri, who is suspended following his dangerous tackle against the All Blacks in Auckland last month.
Meanwhile, Scott Staniforth has been named on the bench, completing a comeback to the Test arena for the second time in his career.
After making his Test debut against the USA during the 1999 World Cup, the 28-year-old Western Force back waited three years before winning his second and third Test caps, in 2002.
Vice-captain Stirling Mortlock and lock Nathan Sharpe will make their 50th appearances for the Wallabies in what will be the team's last game before they embark on a four-Test tour of Europe in October.
Connolly has been delighted with his team's build-up since landing in South Africa last Friday.
"We had a great preparation in Sydney last week and the team has trained very well since we arrived in South Africa," said Connolly.
He admitted he is wary of South Africa following their 21-20 victory over the All Blacks last weekend.
"The Springboks really tightened up their game against the All Blacks and would have gained a considerable confidence boost from the win," he said.
"We know we are in for an extremely tough match and we will need to produce a really strong 80 minutes to beat them."
Australia: Chris Latham; Clyde Rathbone, Stirling Mortlock, Matt Giteau, Cameron Shepherd; Stephen Larkham, George Gregan (capt); Benn Robinson, Jeremy Paul, Rodney Blake, Nathan Sharpe, Dan Vickerman, Rocky Elsom, Phil Waugh, Wycliff Palu.
Replacements: Tai McIsaac, Al Baxter, Mark Chisholm, George Smith, Brett Sheehan, Mark Gerrard, Scott Staniforth.