Wales scrum-half Mike Phillips has been relegated to the bench for Friday's RBS 6 Nations clash against France in Cardiff.
Phillips, who has won 82 caps and was the British and Irish Lions Test number nine in Australia last year, makes way for Rhys Webb, who makes his first Wales start.
As expected, George North moves from wing to centre, where he will partner Jamie Roberts, while Liam Williams takes North's number 11 shirt.
One other change from the side crushed 26-3 by Ireland last time out sees fit-again lock Luke Charteris return instead of Andrew Coombs.
Charteris was sidelined from the Dublin trip due to hamstring trouble, but his comeback should strengthen a Wales lineout that performed poorly at the Aviva Stadium.
Phillips, who has been a mainstay of the Wales team for several seasons and is a double Grand Slam winner, pays the price for an ineffective start to the current Six Nations campaign.
But it still represents a bold selection call by Wales head coach Warren Gatland, despite Webb's impressive form in Ospreys colours.
North, whose previous 37 caps were all won as a starting wing, answers a midfield injury SOS.
Gatland is without the services of Scott Williams, Jonathan Davies and Ashley Beck because of injuries, so he faced an apparent choice between North and James Hook to feature alongside Roberts, but Hook remains on the bench.
And it had been thought Gatland might tinker with the back row, handing Justin Tipuric a start and moving skipper Sam Warburton from openside to blindside flanker, but he has retained the starting trio of Dan Lydiate, Warburton and Taulupe Faletau that was on duty in Dublin.
"Friday is a massive game for us," Gatland said.
"As a squad, we have a huge amount of experience in this tournament, and we will be calling on that this week.
"'We see the game as a huge opportunity for us to put things right.
"Luke (Charteris) has been working really hard over the past couple of weeks, and it's a big boost for us that he is back.
"I thought Rhys (Webb) played excellently for the Ospreys at the weekend, and he comes in and gives us a different dimension. It's a great opportunity for him.
"George (North) moves into the midfield, and he brings great footwork to the role. His partnership with Jamie will be important as we look to stop the directness of France and Mathieu Bastareaud."
The Ireland reversal - Wales' heaviest in the Six Nations since 2006 - dropped them to fourth in the table.
And they must beat France to keep alive any realistic hope of challenging for an unprecedented Six Nations title hat-trick.
France, meanwhile, will arrive in Cardiff following victories over England and Italy, while they have suffered just two defeats from seven previous Millennium Stadium visits in the Six Nations.