Second row Sharpe appears to have paid the price for a disappointing performance in the 39-10 defeat to New Zealand, while Burgess was ruled out after an MRI scan this morning identified a meniscus tear in his knee. The New South Wales Waratahs halfback sustained the injury during a tackle at training yesterday.
"It was an innocuous-looking incident," said Australia coach Robbie Deans.
"Unfortunately, Luke's knee blew up afterwards, was worse again this morning, and the scan has then revealed the bad news."
Injury to Burgess, who is expected to be sidelined for a minimum of four weeks, leaves the Australian touring party with just two No9s - Sam Cordingley and Brett Sheehan.
Three hookers have been included, while injured flanker Rocky Elsom (foot ligament strain) and fullback Adam Ashley-Cooper (broken hand) will also be on tomorrow's flight, with the medical opinion indicating they should be fit for the second Test of the two-game tour.
Australia and South Africa clash twice on successive weekends as the Tri Nations builds to a climax, with the first fixture taking place in Durban on Saturday, August 23 and the second being played in Johannesburg a week later on August 30.
Australia squad to tour South Africa
Stirling Mortlock (Brumbies, captain), Ben Alexander (Brumbies), Adam Ashley-Cooper (Brumbies), Berrick Barnes (Queensland Reds), Al Baxter (NSW Waratahs), Richard Brown (Western Force), Sam Cordingley (Queensland Reds), Ryan Cross (Western Force), Matt Dunning (NSW Waratahs), Rocky Elsom (NSW Waratahs), Adam Freier (NSW Waratahs), Matt Giteau (Western Force), James Horwill (Queensland Reds), Peter Hynes (Queensland Reds), Hugh McMeniman (Queensland Reds), Drew Mitchell (Western Force), Dean Mumm (NSW Waratahs), Stephen Moore (Queensland Reds), Wycliff Palu (NSW Waratahs), Tatafu Polota-Nau (NSW Waratahs), Benn Robinson (NSW Waratahs), Brett Sheehan (NSW Waratahs), George Smith (Brumbies), Timana Tahu (NSW Waratahs), Lote Tuqiri (NSW Waratahs), Lachie Turner (NSW Waratahs), Phil Waugh (NSW Waratahs), Dan Vickerman (NSW Waratahs)