Wallabies coach Michael Cheika has opted to shift Pocock into the number six jersey for the first time in his 61-Test career.
With Dean Mumm out because of a one-week suspension, Wallabies coach Michael Cheika has opted to shift Pocock into the number six jersey for the first time in his 61-Test career.
It will be the tireless flanker's first Test start since breaking his hand in the 36-20 win over Argentina on September 17.
Tevita Kuridrani joins Pocock as the only other change to the starting XV with the Brumbies centre earning the number 13 jersey in the absence of Samu Kerevi.
Kuridrani will partner Reece Hodge in the centres, as the sixth different midfield partnership for the Wallabies in 2016.
Uncapped Waratahs hooker Tolu Latu was named on the replacements bench, hoping to become the Wallabies' 12th debutant of 2016.
James Slipper and Scott Fardy are the other new inclusions on the bench, with the Queensland Reds prop recalled for his first Test since October 1.
"We've got a very new group of players," said Cheika. "It's our 13th debutant in line for a cap this week, off the bench.
"It's a big change, we've got to reinvest in those guys so they understand what it means to be in the Wallabies and how we need to play the game.
"We're hoping to play some of our best football here on Saturday. We've been improving in games as the year's gone on."
After the Cardiff clash Australia face Tests against Scotland, France, Ireland and England, plus a midweek match with the French Barbarians.
The Wallabies will be aiming for a second Grand Slam over the Home Nations, their previous success coming back in 1984.
But Cheika played down any talk of a Grand Slam, saying: "One day at a time.
"Saying 'it's a real hope' or 'it's not a real hope' is going to add nothing to what actually happens. You just go out and try and improve every day. That's what we've been doing."
Australia are on an 11-match winning streak over Wales, their last defeat coming in 2008, but Cheika again denied the statistic meant anything.
"I don't know if anyone's thinking about 12 in a row when you haven't won as many games as we should've won this year," the coach said.
"That hasn't even popped up on anyone's radar. All that stuff is exactly what it is - the past. It gives us nothing on Saturday and gives them nothing either. The two teams on match day, putting their best rugby forward, and the better team will win - that's how it always boils down."
Israel Folau; Dane Haylett-Petty, Tevita Kuridrani, Reece Hodge, Henry Speight; Bernard Foley, Nick Phipps; Lopeti Timani, Michael Hooper, David Pocock; Adam Coleman, Rory Arnold; Sekope Kepu, Stephen Moore (capt), Scott Sio
Replacements: Tolu Latu, James Slipper, Allan Alaalatoa, Rob Simmons, Scott Fardy, Nick Frisby, Quade Cooper, Sefa Naivalu