Pocock has not featured for the Wallabies since injuring his knee in their opening Rugby Championship fixture against the All Blacks in August, with a niggling calf problem further extending his spell on the sidelines.
Despite Pocock's return at the Millennium Stadium at the expense of Michael Hooper, lock Nathan Sharpe will retain the captaincy as he plays his 116th and final Test before retirement.
There are three further alterations to the side that beat Italy 22-19 in Florence last weekend as Kane Douglas returns to the second row after a knee injury in place of the suspended Sitaleki Timani, while Tatafu Polota-Nau takes over at hooker in place of Stephen Moore.
Douglas did not travel to Italy with the squad but remained in London after the win over England to continue his rehab and be with his ill mother.
Nick Phipps also returns to the run-on side in place of Brett Sheehan, who made his first start six years after his debut against the Azzurri before limping off with an ankle problem.
In Sheehan's absence Waratahs' scrum-half Brendan McKibbin is named on the bench after flying into join the squad on Tuesday. If he takes the field McKibbin will become the 42nd player used by coach Robbie Deans during the Wallabies' 15 Tests this season.
Although Hooper acquitted himself superbly in Pocock's absence, being named man-of-the-match in the win over England, Deans is delighted to have his first-choice openside back in his starting XV.
He said: "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.
"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."
Australia team to play Wales at the Millennium Stadium on Saturday, December 1, Kick-off 1430: B Barnes (Waratahs), N Cummins (Western Force), A Ashley-Cooper (Waratahs), B Tapuai (Reds), D Mitchell (Waratahs), K Beale (Melbourne Rebels), N Phipps (Melbourne Rebels); B Robinson (Waratahs), T Polota-Nau (Waratahs), B Alexander (Brumbies); K Douglas (Waratahs), N Sharpe (Western Force, captain); S Higginbotham (Melbourne Rebels), D Pocock (Brumbies), W Palu (Waratahs).
Replacements: S Moore (Brumbies), J Slipper (Reds), S Kepu (Waratahs), D Dennis (Waratahs), M Hooper (Waratahs), B McKibbin (Waratahs), M Harris (Reds), D Ioane (Reds).
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