Scott Sio will make his first career start at loosehead prop in Durban on Saturday, when the Brumbies take on the Sharks.
The 21-year-old is one of five changes to the team which beat the Waratahs in Canberra last week.
George Smith (openside flank), Fotu Auelua (No.8), Tevita Kuridrani (outside centre) and Joe Tomane (wing) have all been added to the starting 15.
With Sio at loosehead, Ben Alexander slides across the scum to tighthead where he is usually seen playing for the Wallabies.
Coincidentally, Sio made his Super Rugby debut off the bench against the Sharks in 2012 and will now make his run-on debut in the same fixture a year later.
Captain Ben Mowen switches from the back of the scrum to blindside flank and Peter Kimlin to lock, while Scott Fardy and Clyde Rathbone drop to the bench.
Ruaidhri Murphy makes his first appearance on the bench since round one, while Andrew Smith and Dan Palmer drop out of the match-day 22.
With David Pocock set to miss the rest of the Super Rugby season, former Australian Under-20 skipper Colby Faingaa will also feature on the Brumbies bench in place of 129-game veteran, George Smith.
Despite being just 21 this is Faingaa's third tour of South Africa, with the young flank keen to leave a big impact once injected from the bench.
Coach Jake White said the 2012 runners-up posed a huge test for his side.
"Traditionally this has been one of the Brumbies biggest games of the season," the former World Cup-winning Springbok coach said.
"To come away from Durban with four points is a huge challenge but one the team feels comfortable with," White added.
"Scotty Sio has been working hard on his set-piece and fitness and it's nice to be able to hand him his first starting jersey.
"Likewise Tevita, Joe and Fotu are proven Super Rugby players and I'm looking forward to seeing those guys in full flight on Saturday. It's nice to be back in Durban, I've always enjoyed my time here and hopefully things stay like that after Saturday."
Brumbies: 15 Jesse Mogg, 14 Henry Speight, 13 Tevita Kuridrani, 12 Christian Lealiifano, 11 Joe Tomane, 10 Matt Toomua, 9 Nic White, 8 Fotu Auelua, 7 George Smith, 6 Ben Mowen (captain), 5 Sam Carter, 4 Peter Kimlin, 3 Ben Alexander, 2 Stephen Moore, 1 Scott Sio.
Replacements: 16 Siliva Siliva, 17 Ruaidhri Murphy, 18 Scott Fardy, 19 Colby Faingaa, 20 Ian Prior, 21 Robbie Coleman, 22 Clyde Rathbone.
Date: Saturday, March 16
Venue: Kings Park, Durban
Kick-off: 17.05 (15.05 GMT)
Referee: Jonathan Kaplan (South Africa)
Assistant referees: Quinton Immelman (South Africa), Reuben Rossouw (South Africa)
TMO: Deon van Blommestein (South Africa)