Hooker and vice-captain Stuart McInally, number eight Magnus Bradbury and second-rower Sam Skinner come into the side, with the latter starting for the first time in the campaign.
Townsend has named the same back division for the third match in a row, with captain Stuart Hogg set to move into joint seventh place on Scotland's all-time appearance list, overtaking Greig Laidlaw and John Barclay to join Jason White and Nathan Hines on 77 caps.
Scotland head into the game in Cardiff on the back of an impressive 28-17 victory over France at Murrayfield which ended the visitors' hopes of the Grand Slam.
"We set out this season to improve our consistency over a run of five tough games, something we have done well so far," Townsend said.
"We've stayed in the fight in every game, which is a credit to how hard the players have worked in training and during the Tests.
"It's also been encouraging to see how well the players have grown together and have taken on board the input from new coaches, Steve (Tandy) and Pieter (De Villiers), who have done a great job in their first season with the team.
"We have huge respect for the Welsh team, who narrowly missed out on a World Cup final a few months ago. They are well coached and have some outstanding players.
"It will be a fantastic occasion and one last opportunity to play to our potential in this championship."