Former England prop Alec Hepburn and fellow front-rower Will Hurd, utility back Harry Paterson and winger Arron Reed were all included for the first time by Townsend.
Hepburn won six caps for England but qualifies through his father, who was born in Scotland, likewise former England junior international Reed.
Townsend is looking to refresh Scotland's front row, which came under pressure during last year's World Cup in France.
"Alec has always been an excellent player. He scrums well and we are delighted he was available for us to select," Townsend said.
"It has really been in the last few months at Leicester that Will has established the type of player he is – a strong scrummager who hits hard in defence and works really hard."
Townsend is also excited to see his new backline recruits in action.
"Aaron has been playing regularly for Sale and I met him on a number of occasions to see where he fitted in on our depth chart. He has moved right up that," Townsend said.
"He brings real effort and speed, with an exciting attacking ability and he is good in defence.
"We have been impressed with Harry, he brings an edge to his game but is an excellent attacker with a good kicking game and can play anywhere in the back three."
The rest of Townsend's squad, for which a captain is still to be named, has much of a familiar look, with 15 players from Glasgow Warriors, 13 from Edinburgh and a further 11 who ply their trade outside Scotland.
A call on the captaincy will be made next week with Jamie Ritchie, who led the team at the World Cup, carrying an injury, though he is expected to recover in time to face Wales.
Scotland squad:
Forwards: Ewan Ashman, Josh Bayliss, Jamie Bhatti, Andy Christie, Luke Crosbie, Scott Cummings, Jack Dempsey, Rory Darge, Grant Gilchrist, Richie Gray, Matt Fagerson, Zander Fagerson, Alec Hepburn, Will Hurd, Johnny Matthews, WP Nel, Jamie Ritchie, Pierre Schoeman, Sam Skinner, George Turner, Glen Young
Backs: Adam Hastings, Ben Healy, George Horne, Darcy Graham, Rory Hutchinson, Huw Jones, Blair Kinghorn, Stafford McDowall, Harry Paterson, Ali Price, Cameron Redpath, Arron Reed, Kyle Rowe, Finn Russell, Kyle Steyn, Sione Tuipulotu, Duhan van der Merwe, Ben White.