Gareth Davies will start at scrum-half for Wales against England in Cardiff on Saturday while Gareth Anscombe gets the nod at fly-half.
Anscombe has been preferred to the more experienced Dan Biggar, while Davies takes over from Tomos Williams, who was not considered due to injury.
That is one of two changes to the side who beat France three weeks ago, with the other seeing Dragons lock Cory Hill replace Adam Beard as skipper Alun Wyn Jones' second-row partner.
Head coach Warren Gatland fielded a much-changed team for the win over Italy last time out, and full-back Liam Williams, wing Josh Adams, centre Jonathan Davies and back-row forward Josh Navidi are the only players who retain their places from Rome.
Davies is one of four players from the side that crushed England's Grand Slam hopes in 2013 - captain Jones, wing George North and flanker Justin Tipuric were also in the line-up for the stunning 30-3 victory.
Wales and England are the tournament's only two remaining unbeaten teams this season, and Saturday's encounter is being billed as a Six Nations title eliminator.
Victory for Wales would make it 12 in succession, breaking their record of 11 games undefeated that was set between 1907 and 1910 - but England have won their last five Six Nations matches against England.
Gatland said: "We are really happy with the experience we have got in the side.
"We have been on the road for the first two weeks, and we are looking forward to being back at home and to build on those first two wins and to build on our performance.
"We've had a great two-week lead up to this game. We've looked really sharp and the squad are incredibly motivated to kick on.
"We know how important this game is for the rest of the championship.
"It's a massive challenge playing against an England team that is playing really well and with a lot of confidence, and we've got to make it difficult for them on Saturday."
Full-back Leigh Halfpenny again misses out following the concussion he suffered three months ago.
Halfpenny, who last played on November 10 when Wales beat Australia, trained with Wales this week but is not involved in the matchday 23.
Wales: 15 Liam Williams, 14 George North, 13 Jonathan Davies, 12 Hadleigh Parkes, 11 Josh Adams, 10 Gareth Anscombe, 9 Gareth Davies, 1 Rob Evans, 2 Ken Owens, 3 Tomas Francis, 4 Cory Hill, 5 Alun-Wyn Jones (captain), 6 Josh Navidi, 7 Justin Tipuric, 8 Ross Moriarty.
Replacements: 16 Elliot Dee, 17 Nicky Smith, 18 Dillon Lewis, 19 Adam Beard, 20 Aaron Wainwright, 21 Aled Davies, 22 Dan Biggar, 23 Owen Watkin.