Lions duo Adam Jones and Alun Wyn Jones have been ruled out through injury, as has inform Dragons lock Luke Charteris who is struggling with a wrist problem.
Scarlets centre Jonathan Davies has groin damage so is replaced by clubmate Scott Williams, while Lions tourists Mike Phillips and James Hook are unavailable following their summer switches to French sides Bayonne and Perpignan.
Gatland was also unable to select World Cup squad members Lee Byrne, Andy Powell and Craig Mitchell following their moves to Clermont Auvergne, Sale Sharks and Exeter Chiefs respectively.
Sam Warburton retains the captaincy ahead of Matthew Rees, with the former skipper named among the replacements.
Ospreys second row Evans Ian Evans returns to the starting line-up after a three year absence, having last featured against New Zealand in November 2008, and Blues prop Scott Andrews is handed his first international start.
Lloyd Williams takes over from Phillips at scrum-half and Rhys Priestland returns at fly-half, while Toby Faletau reverts to No8 having played at openside in Warburton's absence in the final match in New Zealand.
Double Lions tourist Shane Williams is all set for his farewell at the Millennium Stadium having been named on the left wing for his final international, with fellow Lions Leigh Halfpenny, Jamie Roberts and Gethin Jenkins also named in the starting side and Ryan Jones joining Rees on the bench.
There are also spots in the matchday 22 for Ospreys No10 Dan Biggar and flanker Justin Tipuric and Blues wing Alex Cuthbert.
"As we remember the highs and lows of New Zealand and the World Cup, the focus must now be to build for the next four years, the immediate future of the 6 Nations next year and towards the 2015 World Cup," said Gatland.
"Players like Scott Andrews, Ian Evans and Lloyd Williams have an immediate opportunity to impress and the likes of Justin Tipuric, Dan Biggar and Alex Cuthbert have a chance from the bench."
Wales (vs Australia, Millennium Stadium, Saturday, 2.30pm)
Leigh Halfpenny; George North, Scott Williams, Jamie Roberts, Shane Williams, Rhys Priestland, Lloyd Williams; Gethin Jenkins, Huw Bennett, Scott Andrews, Bradley Davies, Ian Evans, Dan Lydiate, Sam Warburton (C), Toby Faletau
Replacements: Matthew Rees, Ryan Bevington, Ryan Jones, Justin Tipuric, Tavis Knoyle, Dan Biggar, Alex Cuthbert
NB Bold denotes Lion