Noah Lolesio (22) will start at flyhalf in place of the dropped James O'Connor (32), while Reece Hodge (27) has been promoted to starting fullback as Rennie looks to his prodigious boot to do damage against the world champions.
"With Hodgey at the back, it gives us a big kicking game which we think will be important," Rennie told reporters on Thursday.
"His ability to identify space and find grass with his big, booming boot is a big reason we picked him."
Hodge's promotion has shunted Tom Wright back to the wing after the ACT Brumbies speedster struggled with the high ball in the 48-17 hiding by Argentina in San Juan.
Andrew Kellaway (26) was considered for a starting role in the back three after recovering from a hamstring injury, Rennie said, but will instead ease in off the bench.
Hooker Folau Fainga'a (27) and inside centre Hunter Paisami (24) will start after recovering from head-knocks, while prop Allan Alaalatoa (28) is also back in the front row after missing San Juan for personal reasons.
Alaalatoa's recall put Taniela Tupou (26) on the bench, and Rennie demanded more from the Queensland Reds tighthead after his subdued display in San Juan.
"He’s well aware of that. He’s pretty disappointed with his effort in the second test," said Rennie.
"We know he’s a very good scrummager but we expect him to dominate with and without the ball."
Matt Philip (28) will start in the second row in place of the demoted Darcy Swain (25), while Dave Porecki (29) is back from concussion to provide hooker cover on the bench.
Loosehead prop James Slipper (33) will lead the side again as regular captain Michael Hooper (30) remains unavailable for wellbeing reasons.
Like the hosts, South Africa will be eager to rebound at Adelaide Oval following their home defeat to the resurgent All Blacks at Ellis Park.
With flyhalf Quade Cooper (34) steering the side, Australia beat the Springboks in back-to-back tests in last year's Rugby Championship.
Cooper is now sidelined with an Achilles injury, though, putting pressure on Lolesio in his first test since being dropped after struggling in the series-deciding defeat by England in Sydney.
"He wasn’t disastrous (against England) but he certainly wasn’t as good as he was in test one," said Rennie.
"He's trained well. Noah’s got an opportunity to try and cement that jersey," said Rennie.
Australia team:
15-Reece Hodge, 14-Tom Wright, 13-Len Ikitau, 12-Hunter Paisami, 11-Marika Koroibete, 10-Noah Lolesio, 9-Nic White, 8-Rob Valetini, 7-Fraser McReight, 6-Jed Holloway, 5-Matt Philip, 4-Rory Arnold, 3-Allan Alaalatoa, 2-Folau Fainga'a, 1-James Slipper (captain)
Replacements: 16-Dave Porecki, 17-Scott Sio, 18-Taniela Tupou, 19-Darcy Swain, 20-Rob Leota, 21-Pete Samu, 22-Tate McDermott, 23-Andrew McKellaway.
