The return of Brumbies star Pat McCabe, who suffered a stress fracture of his leg in the lead up to the Rugby Championship, sees Berrick Barnes move from inside centre to full back, with Kurtley Beale dropped to the bench.
Beale was named the Wallabies' Player of the Year in 2011 but has now been dropped twice in four games despite the fact that Barnes has no representative experience in the No15 shirt.
Nick Phipps of the Rebels is called up for just his second start in place of Genia, while Waratahs lock Kane Douglas will make his debut at Skilled Park.
"Kane has been with us a fair while now, has worked hard and provides us with a similar set-piece presence as Sita does," said Deans, who is confident the changes won't affect the way the Wallabies want to play in their first clash with Argentina since 2003.
"He's a big man so he will help anchor the scrum on the tight-head side in a similar way to how Sita has.
"Kane also has the benefit of plenty of recent match play under his belt in club rugby, which will help make his introduction to Test rugby a little easier.
"Nick's had a good grounding, knows our method and has worked hard.
"He has a great work ethic, is a quality bloke to have in the group as his enthusiasm is infectious, and has handled everything that has been thrown at him as a Test player - including a run as a replacement wing during last year's Rugby World Cup. He's ready to go.
"Berrick has good grounding at the back, while his ability to take just about every point-scoring opportunity on offer (with his goal-kicking) was highlighted once again last weekend.
"Berrick's been kicking very well so he's been an important part of our game turning over the scoreboard.
"His presence provides good balance to the backline, while giving us the opportunity to throw Kurtley in where he will be at his most dangerous, against a tiring defensive line as the game opens up and he can get out there with a license to play."
Stephen Moore has been penciled in for a spot among the replacements after pulling out of last week's win over South Africa with injury. Moore, who will become his country's most-capped hooker if he makes an appearance against the Pumas, faces a late fitness test but won't win his starting place back from Tatafu Polota Nau even if he is given the all clear.
With stand-in skipper Genia joining former captains David Pocock and James Horwill on the sidelines, veteran lock Nathan Sharpe will lead the side on his 109th Test appearance.
Genia's absence has also led to a first Wallaby call up in three years for Brett Sheehan of the Force who steps in to take the spot vacated by Phipps in the matchday 22.
Australia: Berrick Barnes, Dom Shipperley, Adam Ashley-Cooper, Pat McCabe, Digby Ioane, Quade Cooper, Nick Phipps, Radike Samo, Michael Hooper, Dave Dennis, Nathan Sharpe (captain), Kane Douglas, Ben Alexander, Tatafu Polota Nau, Benn Robinson.
Replacements: Stephen Moore/Saia Fainga'a, James Slipper, Scott Higginbotham, Liam Gill, Brett Sheehan, Anthony Fainga'a, Kurtley Beale