Scarlets back row Josh Macleod will make his Wales debut against Georgia in the unfamiliar role of number eight.
Coach Wayne Pivac has made six changes from the side that beat Argentina for the penultimate autumn Test - but there is still no room for Alun Wyn Jones.
Macleod, Ben Carter and Jac Morgan start in the forwards, while Josh Adams, Owen Watkin and Rhys Priestland are named in the backs.
Uncapped duo Dafydd Jenkins and Dane Blacker are among the replacements.
Exeter lock Jenkins, 19, was only called into the squad this week along with Ospreys second row Rhys Davies to cover for the injured Will Rowlands and Dan Lydiate.
Macleod's patience rewarded
Macleod, 26, has waited a long time to be capped. He was selected in the 2020 autumn Test squad but suffered a hamstring injury a day before the players linked up.
He was named in the side to play in the Six Nations in Scotland in February 2021, but an hour later he ruptured his Achilles tendon in a training session - an injury that ruled him out for 11 months.
Macleod replaces Taulupe Faletau, who is named as a replacement, while Morgan comes in for Lydiate.
Macleod's last start at number eight was for Scarlets against Leinster in January 2019.
Specialist number eights like Ross Moriarty, Aaron Wainwright and James Ratti are not involved in the squad.
"Josh is a player that's been really unfortunate in the past," said Pivac.
"We've wanted to use him on a couple of occasions, so this is very much third time lucky for him.
"He covers the back row. We know a lot about him, I've coached him at the Scarlets.
"He brings a lot of energy, he's very strong over the ball and in tandem with Jac Morgan hopefully that will be a strong part of our game on the weekend.
"We're looking forward to seeing him go at this level and seeing the physicality that he will bring."
On Jenkins' selection as a replacement, Pivac added: "Dafydd is a young player that we've had an eye on for quite some time now.
"He's done well with Wales Under-20s and is doing very well at Exeter Chiefs. Talking to Rob Baxter, he's very happy with what Daf is doing.
"Daf captained that side last week so his leadership is valued and already in camp for a very short time he's picked everything up very quickly.
"We're excited to see him go. There's not many players like him in Wales and he's definitely a player for the future and one we think this is the opportunity to have a look at him."
With Louis Rees-Zammit staying at full-back, wing Adams, who replaces Rio Dyer, will start his first game in almost a month after suffering a hand injury while playing for Cardiff.
Fly-half Priestland is named instead of Gareth Anscombe, while centre Watkin starts alongside George North with Nick Tompkins dropping out.
Leigh Halfpenny returns as a replacement after recovering from a hamstring injury.
Wales face Georgia in Cardiff on Saturday, having bounced back from defeat by New Zealand to beat the Pumas.
"Georgia are a side that will be not too dissimilar to Argentina in terms of the forward play, they're very strong up front," added Pivac.
"Traditionally they've been good in the set piece, good driving line-out and very physical.
"We need to back up the performance against Argentina, be a lot more clinical with the ball.
"We've challenged the boys again and I think a response will be what we're looking for on the weekend.
"For us it's about starting well - the last two matches we've gifted the opposition points early - so discipline early on is going to be important."
Wales host Australia on 26 November, which is outside the agreed global Test period and means England-based players will not be available.
Wales team to face Georgia: Rees-Zammit; Cuthbert, North, Watkin, Adams; Priestland, T Williams; G Thomas, Owens, D Lewis, Carter, Beard, J Morgan, Tipuric (capt), J Macleod.
Replacements: B Roberts, R Jones, S Wainwright, D Jenkins, Faletau, Blacker, Costelow, Halfpenny.