Kiss has made a number of adjustments to his squad, including the return of Jordan Petaia after a lengthy absence from international rugby and the inclusion of uncapped fly-half Harry McLaughlin-Phillips.
The Wallabies will assemble in Perth on Friday as they begin preparations for a major challenge against the back-to-back world champions.
Petaia, who recently joined Japan Rugby League One outfit Urayasu D-Rocks, has not represented Australia since the 2023 Rugby World Cup in France.
The 26-year-old left Australian rugby in 2024 to pursue an NFL opportunity and had a trial with the Los Angeles Chargers before returning to rugby with Top 14 side Perpignan. He featured 12 times for the French club during the 2024/25 season.
Petaia made his Wallabies debut as a teenager against Uruguay at the 2019 Rugby World Cup in Japan and was previously regarded as one of Australia's most promising backs.
McLaughlin-Phillips has been added as cover for Carter Gordon, who is sidelined with a leg fracture. The 24-year-old started for the Western Force in the Super Rugby AUS opener last weekend and kicked the winning points against his former club, the Queensland Reds.
The fly-half represented Australia at the 2023 and 2024 World Rugby U20 Championships and was also part of the Wallabies' wider group during their recent Nations Championship Tests against Ireland, France and Italy.
There is also a return from injury for Reds prop Zane Nonggorr, who comes back into the squad after recovering from a calf problem. He replaces Massimo De Lutiis.
Nonggorr's Queensland team-mate Jock Campbell is also included after joining the squad as a late replacement for injured Dylan Pietsch in Argentina.
Australia head into the Perth clash after beating Argentina twice, while South Africa arrive on the back of a 3-1 series victory over New Zealand. The Springboks sealed the series with a 43-28 win over the All Blacks in Baltimore at the weekend.
Kiss knows his side face a major challenge against the world's leading team.
"We've learned a bit more about ourselves as a group over the last four Tests, and we know we still have a lot to work on to get to where we want to be," he said.
"South Africa have been the benchmark team in World Rugby for a long time, and we're motivated by the challenge of meeting them in our own backyard in two weeks' time."
Wallabies squad for the Test against the Springboks
Forwards: Allan Alaalatoa, Angus Bell, Charlie Cale, Josh Canham, Tom Hooper, Isaac Kailea, Fraser McReight, Josh Nasser, Zane Nonggorr, Brandon Paenga-Amosa, Billy Pollard, Aidan Ross, Lukhan Salakaia-Loto, Lachlan Shaw, Carlo Tizzano, Taniela Tupou, Rob Valetini, Jeremy Williams, Harry Wilson (c).
Backs: Jock Campbell, Ben Donaldson, Isaac Henry, Len Ikitau, Max Jorgensen, Ryan Lonergan, Tate McDermott, Harry McLaughlin-Phillips, Declan Meredith, Hunter Paisami, Jordan Petaia, Harry Potter, Joseph-Aukuso Suaalii, Kalani Thomas, Tom Wright.