Gareth Anscombe will make his first Wales start since 2019 when they face New Zealand, the country of the fly-half's birth, in Cardiff on Saturday.
Anscombe, 30, has impressed for Ospreys after two years out with a knee injury.
There is also a first start for 21-year-old flanker Taine Basham in an all-Dragons back row alongside Ross Moriarty and Aaron Wainwright.
Hooker Ken Owens was initially named in the team but has failed a fitness test so is replaced by Ryan Elias.
Kirby Myhill, called into the squad as injury cover for Elliot Dee, takes Elias' place on the bench.
Scarlets full-back Liam Williams misses out as he continues to recover from surgery to remove his appendix.
Cardiff flanker Ellis Jenkins is also absent after injuring a rib earlier this month.
Jenkins and Williams had hoped to be fit in time to face the All Blacks but their absence means Wales will be without 19 players on Saturday.
Several players are injured and English clubs are not releasing their players because the game has been arranged outside World Rugby's international window, while Cardiff centre Willis Halaholo contracted Covid-19 this week.
Captain Alun Wyn Jones will lead Wales as they play in front of a capacity home crowd for the first time since February 2020 due to the Covid-19 pandemic.
Jones, 36, will play his 149th international for Wales, surpassing the previous record for one country set by New Zealand legend Richie McCaw.
Anscombe returns to Test rugby two years after suffering a serious knee injury while playing for Wales against England in a warm-up match for the 2019 World Cup.
He has only started four games this season, including one friendly, but has impressed enough to earn a recall alongside scrum-half Tomos Williams.
Anscombe played for New Zealand at Under-20 level before moving to Wales, who he qualifies for through his Cardiff-born mother Tracy.
He has 27 Wales caps but has only made one replacement appearance against the All Blacks in 2016.
Anscombe and Rhys Priestland were the two fly-half options, with English-based duo Dan Biggar and Callum Sheedy unavailable.
Priestland, 34, last featured at international level against New Zealand in November 2017 and is eligible for selection again after returning to Wales to join Cardiff from Bath.
Northampton's Biggar and Bristol's Sheedy and fellow England-based players Louis Rees-Zammit, Taulupe Faletau, Nick Tompkins, Thomas Young and Christ Tshiunza were unavailable to play against the All Blacks.
Head coach Wayne Pivac has a long list of absentees in the back row. Justin Tipuric, Josh Navidi, Ellis Jenkins, James Botham, Josh Macleod, Dan Lydiate and James Davies are injured, with Young and Faletau also missing for the New Zealand fixture.
Basham, 21, made three replacement appearances in the summer against Argentina and Canada but is given a starting spot after a storming start to the season.
With Leigh Halfpenny ruled out until next year, Williams out for this weekend and Rees-Zammit unavailable, New Zealand-born Johnny McNicholl is handed a first start at full-back alongside wings Owen Lane and Josh Adams in the back three.
With George North missing the autumn series through injury and Halaholo absent, Johnny Williams and Jonathan Davies form an all Scarlets centre partnership.
"With injuries and unavailability it's another great opportunity for players like Taine Basham and Ben Thomas to come into the group and gain valuable experience," said head coach Wayne Pivac.
"They're going to come away from this test match knowing what it's like to play one of the best teams in the world.
"To win a World Cup you have to play against teams like New Zealand at some stage in the tournament and you have to win those games.
"It's going to be a great experience for those guys who haven't played a lot of test rugby and they'll certainly know they've been in a match afterwards."
Wales: Johnny McNicholl; Owen Lane, Jonathan Davies, Johnny Williams, Josh Adams; Gareth Anscombe, Tomos Williams; Wyn Jones, Ryan Elias, Tomas Francis, Adam Beard, Alun Wyn Jones (capt), Ross Moriarty, Taine Basham, Aaron Wainwright.
Replacements: Kirby Myhill, Rhys Carre, Dillon Lewis, Will Rowlands, Seb Davies, Gareth Davies, Rhys Priestland, Ben Thomas.