Louis Rees-Zammit will start at fullback in Wales’ Autumn Nations Series clash with Argentina on Saturday.
He switches from the wing to fill a problem position for Wales, with Liam Williams and Leigh Halfpenny both injured.
Rees-Zammit made his Test debut after going on as a second-half substitute for Halfpenny against France in 2020, but the Gloucester speedster’s subsequent 19 appearances were all on the wing.
Alex Cuthbert, who has recovered from injury, completes the back three alongside Rio Dyer, a try-scorer on his Test debut when New Zealand beat Wales 55-23 last weekend.
Gareth Anscombe, who deputised for Halfpenny five days ago, reverts to outhalf, replacing Rhys Priestland.
Elsewhere, prop Dillon Lewis starts instead of Tomas Francis and experienced Ospreys flanker Dan Lydiate features in the backrow.
With Leicester flanker Tommy Reffell sidelined because of a rib injury, captain Justin Tipuric moves across to openside, packing down with number eight Taulupe Faletau in a backrow trio boasting 246 caps.
There is no place in the matchday 23 for Wales’ record cap holder Alun Wyn Jones, as Ben Carter provides secondrow cover, with other bench changes seeing props Rhodri Jones and Sam Wainwright selected, plus Priestland and Ospreys flanker Jac Morgan.
Wales head coach Wayne Pivac said: “Last week we had Leigh Halfpenny unavailable at the last minute and we had trained a certain way, so we went with Gareth Anscombe at full-back, who has done that before at this level.
“We are back to Gareth at 10, and we have Louis Rees-Zammit at fullback. He (Rees-Zammit) has trained there the entire week.
“He has looked good in training and it is something we’ve explored in the background, so it will be good information going forwards with the Six Nations around the corner and the Rugby World Cup.
“Dillon did well in South Africa. This is probably the last opportunity to give guys starts and learn as much as we can. Both Dillon and Dan Lydiate have trained well.
“There are some changes among the replacements. There are some niggles that players pick up in games and in training, so some guys have been left out to get themselves 100 per cent right for next week.
“Some boys we want to have a look at across the competition, so in the case of Nicky Smith and Rhodri Jones that is certainly what we wanted to do in the first couple of games.”
On the decision to leave out secondrow Jones, Pivac added: “It’s an opportunity before the Six Nations and World Cup to give Ben Carter a chance. If they’re called upon in the Six Nations or World Cup, they need to be exposed. We think this is that opportunity.
“We speak to all the players on a regular basis. We set goals for the season and Al is no different. Each player is reviewed and we’ll talk on goals. We have a great relationship. It’s a goal for everybody to get to the World Cup. Each player will have steps to take.”
Argentina have arrived in Cardiff on the back of a 30-29 victory over England, which was their first win at Twickenham for 16 years.
Pivac added: “We saw last week what Argentina are capable of. They are a very big team, very strong up front.
“They have expanded their attacking game and they took an excellent try against England from set-play. They’ve knocked over some big scalps in the last 18 months, New Zealand being one of them.
“They are going to be a big challenge, but one we are looking forward to. After last week’s performance we need a reaction from our team.”
Wales: Louis Rees-Zammit; Alex Cuthbert, George North, Nick Tompkins, Rio Dyer; Gareth Anscombe, Tomos Williams; Gareth Thomas, Ken Owens, Dillon Lewis; Will Rowlands, Adam Beard; Dan Lydiate, Justin Tipuric, Taulupe Faletau.
Replacements: Ryan Elias, Rhodri Jones, Sam Wainwright, Ben Carter, Jac Morgan, Kieran Hardy, Rhys Priestland, Owen Watkin.