The former Wallabies captain has not played since the opening Rugby Championship match against New Zealand in August during which he injured his knee.
He was scheduled to play earlier in the tour but suffered a minor calf strain in Paris. His replacement Michael Hooper has been dropped to the replacements' bench.
"David is one of the best in the world as a player, and is growing every day as a leader, so naturally we are delighted to have him back," coach Robbie Deans said in an Australian Rugby Union (ARU) statement.
"While he has continued to contribute off the field, this tour has been one of frustration for him, but we were not prepared to take any risks and potentially compromise either the player or the team, in terms of his fitness.
"The upside to the wait is that his return comes at a time where we need fresh energy, as was evident at times during our Test in Italy last weekend."
Nathan Sharpe will retain the captain's armband in his 116th and final Test.
In other changes from the 22-19 win over Italy in Florence, lock Kane Douglas returns from a knee injury in place of the suspended Sitaleki Timani and hooker Tatafu Polota-Nau comes in for Stephen Moore.
After losing to France in Paris, the Wallabies have beaten England and Italy, while Wales have suffered defeats to Argentina, Samoa and New Zealand.
Australia have won their last seven Tests against Wales but Deans expects the hosts to come out fighting.
"You don't win two Grand Slams in the last four years (2008 and 2012) while also making the semi-finals of the Rugby World Cup without being a quality outfit, and a resilient one," he said.
"If we were in their situation, I know the response I would be expecting."
Australia team: 15-Berrick Barnes, 14-Nick Cummins, 13-Adam Ashley-Cooper, 12-Ben Tapuai, 11-Drew Mitchell, 10-Kurtley Beale, 9-Nick Phipps, 8-Wycliff Palu, 7-David Pocock, 6-Scott Higginbotham, 5-Nathan Sharpe (captain), 4-Kane Douglas, 3-Ben Alexander, 2-Tatafu Polota Nau, 1-Benn Robinson.
Replacements: 16-Stephen Moore, 17-James Slipper, 18-Sekope Kepu, 19-Dave Dennis, 20-Michael Hooper, 21-Brendan McKibbin, 22-Mike Harris, 23-Digby Ioane.