Stephen Jones is partnered at half-back by Gloucester scrum-half Gareth Cooper, who is the incumbent in the jersey after impressing on Wales' summer tour to South Africa this June, and Jamie Roberts is selected at outside-centre to form a new partnership in midfield with Gavin Henson.
IRB World Player of the year candidate Shane Williams joins Halfpenny in a back three completed by Lee Byrne and fellow nominee captain Ryan Jones switches to blindside flanker to accommodate Powell at No 8 - with Martyn Williams providing the missing link in the back row.
In the second row Ian Evans is preferred to Ospreys colleague Ian Gough alongside Alun-Wyn Jones and in the front row Gethin Jenkins and Adam Jones pack down either side of Scarlets hooker Matthew Rees.
"Both of the debutants have been form players so far this season so they now get a chance to test themselves against the very best team in the world," said Gatland.
"At 19 years-old our message to Leigh has been to just go out there and enjoy himself, he needs to not worry about his opposite number, but just relax and play without fear and enjoy the experience.
"Andy Powell is a little different as he has been around for a while and is an experienced head, despite his lack of international caps, but he is most definitely in form. We will be looking to get the ball in his hands and see him run.
"Ryan Jones is adept on either side of the scrum, but to switch our captain does tell you a little bit about what we think of Andy.
"At scrum-half Gareth Cooper is the man in possession of the shirt after doing well for us, particularly in the second Test on tour this summer and he has been rewarded.
"In the centres Jamie Roberts and Gavin Henson form a partnership that any side would be proud of, but perhaps the most important point about this selection is the bench.
"We have plenty of talent and experience available to us to come on and change things if necessary, which was something that worked for us in the 6 Nations last season. The likes of Ian Gough, Duncan Jones, Richard Hibbard, Dafydd Jones, Dwayne Peel, James Hook and Tom Shanklin are all able to offer up something different when required."
WALES: Lee Byrne; Leigh Halfpenny, Jamie Roberts, Gavin Henson, Shane Williams; Stephen Jones, Gareth Cooper; Gethin Jenkins, Matthew Rees, Adam Jones, Alun-Wyn Jones, Ian Evans, Ryan Jones (capt), Martyn Williams, Andy Powell REPLACEMENTS: Richard Hibbard, Duncan Jones, Ian Gough, Dafydd Jones, Dwayne Peel, James Hook, Tom Shanklin