Ellis Jenkins is set to make his first Wales appearance in three years in Saturday's match at home to world champions South Africa.
The Cardiff flanker suffered a serious knee injury during Wales' 2018 Autumn win over the Springboks and was sidelined from all rugby for more than two years.
But he now returns to Test duty among six changes following Wales' 54-16 defeat by New Zealand in their Autumn Nations Series opener in Cardiff last weekend.
Jenkins has replaced Ross Moriarty, who suffered a shoulder injury against the All Blacks, in the back row.
Meanwhile, Will Rowlands takes over in the second row from Wales captain Alun Wyn Jones after the veteran lock also sustained a shoulder injury against New Zealand that will require surgery.
Experienced centre Jonathan Davies will lead Wales in Jones' absence, with wing Louis Rees-Zammit and fly-half Dan Biggar -- who both missed the New Zealand match after their England-based clubs refused to release them for a Test outside World Rugby's designated window -- returning to the back division.
Jones, one shy of 150 Wales caps, and Moriarty are among several British and Irish Lions unavailable to Wales coach Wayne Pivac, with that list including George North, Taulupe Faletau, Justin Tipuric, Josh Navidi and Ken Owens.
Pivac said Thursday he expected Jones, who injured the same shoulder prior to leading the Lions in South Africa earlier this year, to miss the whole of Six Nations champions Wales' title defence.
"I don't think he will be available for the Six Nations," Pivac, whose side begin the Championship against Ireland in Dublin on February 5, told a press conference.
"It is on others to step up now," added the New Zealander, who said he thought Jones, the most-capped international in rugby union history with 161 Test appearances, would return before the end of the season.
Meanwhile, Pivac has recalled Saracens centre Nick Tompkins despite Jonny Williams scoring a try against the All Blacks, with Rhys Carre replacing Lions loosehead prop Wyn Jones.
Wales have won their last four Tests at home to South Africa, with the Springboks' last victory in Cardiff coming in 2013.
South Africa named their team on Tuesday for what will be the Springboks' first match since they beat New Zealand 31-29 in the southern hemisphere Rugby Championship last month.
"South Africa coming to town, as world champions, offers a different challenge to New Zealand," said Pivac.
"They have got a massive forward pack -- they are big across the park, really -- and they bring a huge aerial threat, so it is going to be a different challenge."
Johnny McNicholl; Louis Rees-Zammit, Jonathan Davies (capt), Nick Tompkins, Josh Adams; Dan Biggar, Tomos Williams; Aaron Wainwright, Taine Basham, Ellis Jenkins; Adam Beard, Will Rowlands; Tomas Francis, Ryan Elias, Rhys Carre
Replacements: Bradley Roberts, Wyn Jones, WillGriff John, Ben Carter, Seb Davies, Gareth Davies, Gareth Anscombe, Liam Williams
Coach: Wayne Pivac (NZL)