Scotland head coach Gregor Townsend has been forced into rotating his side due to injury with Jamie Ritchie, Sean Maitland and Cameron Redpath all ruled out.
All three players were excellent as Scotland started their campaign with an 11-6 win over England at Twickenham.
Scarlets back-row Blade Thomson, wing Darcy Graham and centre James Lang come in.
Townsend said: “We have an opportunity this weekend against Wales to continue the positive start to the Guinness Six Nations we made last week against England.
“It was a very encouraging performance at Twickenham and the squad performed to a level which has to be the benchmark throughout the tournament.
“Wales are also coming into this game after a win and will have the same objective, so it will be a tough challenge as always.
“Both teams were involved in physical contests last weekend and that is evidenced by the injuries Wales and we ourselves have picked up.
“For us, we are able to bring in three quality players in Blade, James and Darcy. They have been training well and are highly motivated to make the most of this opportunity.”
Scotland ended their 2020 Six Nations with a 14-10 success over Wales in Llanelli.
Townsend’s side are chasing a fifth consecutive Six Nations win this weekend.
You can keep in touch with both camps as we head for round two of the Guinness Six Nations for the Scotland v Wales clash on Saturday – we’ve got interviews, videos and social posts covered right here.