Prop Slipper had been under an injury cloud after picking up a knee problem in training, prompting team officials to rush Brumbies rookie Blake Schoupp to South Africa.
But the influential captain will lead the team in the cauldron of Loftus Versfeld, where the visitors are seeking a first win at the seventh attempt.
"It has been a challenging week, but I get to run today and make sure it is all good. I'm confident I will be fine," Slipper told reporters.
Blindside flanker Tom Hooper, who can also play in the second row, will make his debut at the back of the scrum alongside co-captain Michael Hooper, while Rob Valetini is in at number eight.
Three players who cold make their debuts as ‘finishers’ off the bench are tighthead prop Zane Nonggorr, lock Richie Arnold and flyhalf Carter Gordon.
The front row will see Slipper earn a 128th cap alongside hooker David Porecki and fellow prop Allan Alaalatoa. Nick Frost and Will Skelton make up the lock pairing.
Scrumhalf Nic White raised the ire of South Africans in the Rugby Championship meeting in Adelaide last year and is sure to get a hot reception in Pretoria.
He lines up with flyhalf Quade Cooper, who has returned from an Achilles injury.
The big boot of Reece Hodge, so important at altitude, is at centre and will partner Len Ikitau, while wing Suliasi Vunivalu earns a first Wallabies start with Marika Koroibete on the other flank and Tom Wright at fullback.
"As a squad, the players have worked extremely hard since coming together as a group and we’ve prepared well this week," Jones said in a media release from Rugby Australia.
"The 23 players selected have an opportunity to be part of history with a win over South Africa in Pretoria on Saturday night."
Australia team:
1-James Slipper (captain), 2-David Porecki, 3-Allan Alaalatoa, 4-Nick Frost, 5-Will Skelton, 6-Tom Hooper, 7-Michael Hooper, 8-Rob Valetini, 9-Nic White, 10-Quade Cooper, 11-Marika Koroibete, 12-Reece Hodge, 13-Len Ikitau, 14-Suliasi Vunivalu, 15-Tom Wright
Replacements:
16-Jordan Uelese, 17-Matt Gibbon, 18-Zane Nonggorr, 19-Richie Arnold, 20-Pete Samu, 21-Tate McDermott, 22-Samu Kerevi, 23-Carter Gordon.