Ospreys' Dan Lydiate has been named by Wayne Pivac in his side to face Ireland on Sunday in the flanker's first appearance for the national side since November 2018.
The call-up is a reward for his recent form and he will be joined by Justin Tipuric and Taulupe Faletau in an all-British and Irish Lions back-row.
"We are looking forward to kicking off our campaign this weekend and putting into action two really good training weeks," Wales head coach Wayne Pivac said in a statement.
"We made strides forward through the autumn and we are looking to take that into Sunday and into this tournament.
"The Six Nations is a fantastic tournament and is important for us rugby wise but it is important for so much more this year."
The second-row will consist of captain Alun Wyn Jones and Adam Beard.
Ken Owens, who missed the Autumn Nations Cup and postponed 2020 Six Nations games due to injury, returns to the side and lines up alongside Wyn Jones and Tomas Francis.
Tomos Williams also returns from injury at half-back with Dan Biggar.
George North is on the cusp of his 100th cap with Sunday marking his 99th for Wales. He is joined by Johnny Williams in the cnetre.
Hallam Amos, Louis Rees-Zammit and Leigh Halfpenny make up the rest of the squad.
Wyn Jones, Ken Owens, Tomas Francis, Adam Beard, Alun Wyn Jones, Dan Lydiate, Justin Tipuric, Taulupe Faletau, Tomos Williams, Dan Biggar, Hallam Amos, Johnny Williams, George North, Louis Rees-Zammit, Leigh Halfpenny.
Replacements: Elliot Dee, Rhodri Jones, Leon Brown, Will Rowlands, Josh Navidi, Gareth Davies, Callum Sheedy, Nick Tompkins.