Rhys Webb is back for Wales at scrum-half against Italy in Rome on Saturday, his first Six Nations start since 2017.
The 34-year-old replaces Tomos Williams having last begun a Test three years ago while Rio Dyer takes over on the wing from Louis Rees-Zammit.
Wales coach Warren Gatland also brings in Dafydd Jenkins, Jac Morgan, Liam Williams and prop Wyn Jones.
Lock Alun Wyn Jones, Christ Tshiunza, Leigh Halfpenny miss out while Gareth Thomas drops to the bench.
Dan Biggar has been ruled out by a back problem so Owen Williams continues at fly-half for winless Wales, with versatile Joe Hawkins providing stand-off cover while starting at centre.
Veteran Ospreys lock Jones is also out of the squad with his 22-year-old team-mate Rhys Davies on the bench to back-up regional colleague Adam Beard and Exeter’s Jenkins.
Ospreys prop Thomas drops to the bench, where George North, 30, will also be among the replacements as cover for Wales’ 20-year-old centres Hawkins and Mason Grady.
Wales’ back play will be heavily influenced with Webb and Owen Williams at half-back with Hawkins the inside centre playmaker.
Gatland said: “We feel that having watched Italy and how they’ll tend to play from everywhere, including their own 22, getting guys on the ball is going to be pretty important.
“But he still hasn’t played a lot of rugby in terms of coming back from a relatively long injury with his ankle and we just felt with the way the game’s going to be and the pace of the game, that him coming off the bench and the impact he can have could be pretty important.
Wales: Liam Williams; Josh Adams, Mason Grady, Joe Hawkins, Rio Dyer; Owen Williams, Rhys Webb; Wyn Jones, Ken Owens (capt), Tomas Francis, Dafydd Jenkins, Adam Beard, Jac Morgan, Justin Tipuric, Taulupe Faletau.
Replacements: Scott Baldwin, Gareth Thomas, Dillon Lewis, Rhys Davies, Tommy Reffell, Tomos Williams, George North, Louis Rees-Zammit.
