Harris will make his first start for Scotland against Wales after Townsend named the Newcastle man at outside centre, where he will partner Huw Jones.
Former captain Greig Laidlaw has been named on the bench, with Ali Price preferred at scrum-half after an impressive showing in the autumn internationals, while Jon Welsh and Gordon Reid are recalled following a number of front-row injuries.
Stuart Hogg returns at full-back after missing the impressive win over Australia due to a hip injury suffered in the warm-up.
Harris made his only appearance for the Dark Blues to date off the bench against Samoa, and Townsend is confident he can play a big role in defence at Cardiff in the absence of Alex Dunbar, who has concussion.
“We’ve been really impressed with him overall,” he said. “He’s been very consistent.
“Defensively he’s stood out — and a massive part of winning games, being successful, is having a strong defence, and he’s shown that this year.
“We’ve been really impressed with him in the last two or three weeks before coming to camp, and with the unavailability of Alex Dunbar and Duncan Taylor, he gets an opportunity to start for us at 13.”
Confidence is high in the Scottish camp ahead of what many are rating as their best chance to compete in a Six Nations for a long time following an impressive start to life under Townsend.
Since taking over last summer, the former Glasgow coach has led them to two wins over Australia as well as taking New Zealand right to the wire. Their preparations for this year’s tournaments have been hampered by a number of injuries to the front row, with the likes of Darryl Marfo, Zander Fagerson, WP Nel and Al Dickinson all missing.
Townsend admitted his side has been laid low by injuries, but is confident they still have the players to compete in Cardiff.
He said: “We had injuries in November, and players that were uncapped really stood out well and grabbed their opportunities.
“Darryl, who played so well in November, isn’t available now, but Jamie Bhatti is, and he was outstanding in November.
“But we’ve also got players coming back that are available to us, Gordon Reid specifically, and Jon Welsh has been very consistent for Newcastle.
“We believe we’ve got a really strong scrummaging unit, with two players that can scrum and also add impact off the bench in Jamie and Murray McCallum in the loose in the second half.”
On the decision to pick Price over Laidlaw, he added: “It was always going to be very tight for Greig. He’s done very well to be in our squad, and to come back from injury a week ago.
“To play 80 minutes at the weekend showed to us that he was capable of coming back into our squad, which was good news for Greig and good news for us.”
Meanwhile Alec Hepburn is poised to make his England debut in Sunday’s NatWest 6 Nations opener against Italy in Rome.
The Exeter prop has been included in a 25-man squad retained for the Stadio Olimpico showdown and is set to provide loosehead cover from the bench for Mako Vunipola.
Hepburn, 25, is effectively England’s sixth choice in the position with Joe Marler suspended and Ellis Genge, Mat Mullan and Beno Obano in the treatment room.
On the other side of the scrum Harry Williams will be given the opportunity to add to his five caps in the absence of Kyle Sinckler, who is missing with a hamstring injury, behind starting tighthead Dan Cole.
Chris Robshaw, Maro Itoje and Mike Brown are present after recovering from their respective back, hip and eye problems and Ben Te’o also features having completed his rehabilitation from a high ankle sprain.
M Brown (Harlequins), N Earle (Saracens), J May (Leicester), A Watson (Bath)
D Care (Harlequins), O Farrell (Saracens), G Ford (Leicester), J Joseph (Bath), J Nowell (Exeter), B Te’o (Worcester), B Youngs (Leicester)
G Graham (Newcastle), M Itoje (Saracens), G Kruis (Saracens), C Lawes (Northampton), J Launchbury (Wasps), C Robshaw (Harlequins), S Simmonds (Exeter), S Underhill (Bath)
D Cole (Leicester), J George (Saracens), D Hartley (Northampton), A Hepburn (Exeter), M Vunipola (Saracens), H Williams (Exeter).