George North will start at outside centre in Wales' Six Nations opener against Italy, with uncapped Johnny McNicholl taking his place on the wing.
This will be North's fifth start at centre in his 92nd Test, with Wales struggling with injuries in midfield.
New Zealand-born McNicholl, Wales-qualified through residency, plays his first Test after scoring a try in last year's uncapped win over Barbarians.
Tomos Williams is preferred to the returning Rhys Webb at scrum-half.
Saturday's match at Cardiff's Principality Stadium will be Wayne Pivac's first Test since succeeding Warren Gatland as head coach of the reigning Six Nations champions.
Webb returns for his first Wales game since December 2017 on the replacements bench, with Gareth Davies failing to shake off a late injury.
The centre vacancy for North has been created with British and Irish Lions team-mate Jonathan Davies missing the tournament through a knee injury and Owen Watkin still returning to fitness from his own knee problem.
Saracens centre Nick Tompkins is in line to win his first Wales cap after being named on the bench.
Former England Under-20s centre Tompkins, 24, qualifies through his Welsh grandmother who was born in Wrexham.
There is no room in the 23-man squad for Gloucester 18-year-old wing Louis Rees-Zammit.
Elsewhere, number eight Taulupe Faletau returns for his first international in almost two years.
Faletau's most recent Test match was against France in March 2018 and he was then sidelined by a succession of arm and collarbone injuries which forced him to miss the 2019 World Cup in Japan.
Aaron Wainwright and Justin Tipuric join Faletau in the back row, while Cardiff Blues flanker Josh Navidi will miss the start of the Six Nations with a hamstring injury.
With Tomas Francis injured, Dillon Lewis starts at tight-head prop alongside Scarlets duo Wyn Jones and Ken Owens in the front row.
Tight-head prop Leon Brown will make his tournament debut from the bench, while Jake Ball joins captain Alun Wyn Jones in the second row.
"I'm happy with the side and looking forward to this weekend," said Pivac.
"It is great for Johnny McNicholl to get his first cap. I thought he played really well against the Barbarians so it is a great opportunity for him this weekend.
"George has had a number of games in the midfield for Wales and more recently for the Ospreys and he has been running there in training. We have been impressed with him there and he is excited by the opportunity.
"Nick [Tompkins] has trained well and has impressed and we are looking forward to seeing him at some stage during the game.
"We've had a couple of injuries. Josh Navidi picked up a hamstring injury so he is out for a few weeks, while Liam Williams, Owen Watkin, Gareth Davies and Elliot Dee weren't quite ready to be available for selection.
"The whole team has a great vibe and we are looking forward to getting out there in front of our home supporters on Saturday."
Wales team to face Italy
Leigh Halfpenny; Johnny McNicholl, George North, Hadleigh Parkes, Josh Adams; Dan Biggar, Tomos Williams; Wyn Jones, Ken Owens, Dillon Lewis, Jake Ball, Alun Wyn Jones (capt), Aaron Wainwright, Justin Tipuric, Taulupe Faletau.
Replacements: Ryan Elias, Rob Evans, Leon Brown, Cory Hill, Ross Moriarty, Rhys Webb, Jarrod Evans, Nick Tompkins.