Horwill missed most of last season after surgery to repair a ruptured right hamstring, an injury sustained in a Super Rugby match for Queensland. It sparked a terrible run for players who captained the Wallabies, with both David Pocock and Genia later sustaining season-ending injuries and 2012 ending with veteran lock Nathan Sharpe leading the team.
Genia has filled in as Australia captain three times, including a 26-19 win over South Africa in Perth last year, and has established himself as the regular backline general.
"Will is a proven leader and has had plenty of success as captain for the Queensland Reds and also for Australia," Wallabies coach Ewen McKenzie said. "He is a player that thrives with the added responsibility and he has always stepped up when given the opportunity to lead. I'm sure this will bring the best out of him."
With second row stocks low due to injuries to Hugh McMeniman and Peter Kimlin, Sitaleki Timani is expected to be added to Australia's training squad for the following test against Argentina.
Revised Wallabies squad to play South Africa: Israel Folau, Nick Cummins, Adam Ashley-Cooper, Christian Lealiifano, James O'Connor, Quade Cooper, Will Genia (captain); Ben Mowen, Michael Hooper, Scott Fardy, Kane Douglas, Rob Simmons, Sekope Kepu, Stephen Moore, James Slipper. Reserves: Saia Fainga'a, Scott Sio, Ben Alexander, Ben McCalman, Jake Schatz, Nic White, Matt Toomua, Jesse Mogg.