Winnett had been a doubt with a jaw injury that threatened to rule him out of the first few games of the Six Nations, but he has recovered in time to play.
"Cameron is just a lovely footballer and I think he’s going to develop into a quality international player in the future," Wales coach Warren Gatland said.
"He’s young and there’ll be no pressure on him. He’s done really well in training and following consultation with his surgeon everyone was happy for him to be selected."
The starting lineup features seven players who began Wales’ last international, a 29-17 Rugby World Cup quarter-final loss to Argentina in October, with injury and retirements forcing Gatland’s hand to some degree.
Josh Adams and Rio Dyer are on the wings with Louis Rees-Zammit having left rugby to try his hand at American Football, and Nick Tompkins and Owen Watkin are the centre pairing.
The latter makes his first Wales appearance since 2022 in the absence of the injured George North.
Gareth Davies gets the nod at scrum-half in a line-up that features Wales' second youngest captain ever, 21-year-old lock Dafydd Jenkins, with only Gareth Edwards ahead of him on the list.
Jenkins is in the second row with Adam Beard, and ahead of them are props Corey Domachowski and Leon Brown, with Ryan Elias at hooker.
The back row is made up of number eight Aaron Wainwright, and flankers James Botham, his first test for over two years, and Tommy Reffell.
"We’ve got some players who were involved in the World Cup, so have some experience and then some exciting youngsters and when I look at that forward pack, it’s not a small forward pack. It’s a big forward pack," Gatland said.
Among the Wales replacements, back row Alex Mann could make his first senior international appearance.
Gatland confirmed visitors Scotland have requested the Principality Stadium roof be open.
"I think it’s a little bit disappointing from an atmosphere point of view. But that’s the decision that they made," he said.
Wales team:
15-Cameron Winnett, 14-Josh Adams, 13-Owen Watkin, 12-Nick Tompkins 11-Rio Dyer, 10-Sam Costelow, 9-Gareth Davies; 1-Corey Domachowski, 2-Ryan Elias, 3-Leon Brown, 4-Adam Beard, 5-Dafydd Jenkins (captain), 6-James Botham, 7-Tommy Reffell, 8-Aaron Wainwright
Replacements: 16-Elliot Dee, 17-Kemsley Mathias, 18-Keiron Assiratti, 19-Teddy Williams, 20-Alex Mann, 21-Tomos Williams, 22-Ioan Lloyd 23-Mason Grady,
For Scotland, Russell forms a half-back pairing with number nine Ben White, while Sione Tuipulotu and Huw Jones are reunited in the midfield and there is a back three of wings Duhan van der Merwe and Kyle Steyn, with Kyle Rowe at full-back. The latter takes the number 15 jersey with Blair Kinghorn ruled out of the first two games of the championship through injury.
"Blair played on Sunday for Toulouse and picked up a knee injury," Scotland coach Gregor Townsend said. "We thought he would be good to go for the weekend, but after having a scan, he will miss the first two games of the championship.
"While that is a blow for Blair, it is an opportunity for Kyle, who has been in great form for Glasgow and someone we have been looking at as full-back cover."
The front row of the scrum contains hooker George Turner, with props Pierre Schoeman and Zander Fagerson either side of him. There are two potential prop debuts among the replacements, with Alec Hepburn and Elliot Millar-Mills on the bench.
Richie Gray and Scott Cummings are the lock pairing, while former captain Jamie Ritchie is selected on the side of the scrum alongside fellow flanker Luke Crosbie, with Matt Fagerson at number eight.
"Rory is in from the final stages of his rehab, this game came too soon for him but he will be back next week," Townsend said. "We have gone for experienced players (in the back row) that have played together and that we believe are in form.
"They know they have this opportunity and they will have to play well. It is probably the area of the pitch where we have the most depth in the squad."
Townsend is expecting a typically physical confrontation from what is a relatively inexperienced Wales side.
"There will be physicality, Wales always play with passion, target the ruck area in attack and defence. We expect to be tested there," he said.
Scotland are seeking a first win in Cardiff since 2002, though they did claim a 14-10 victory in front of empty stands in Llanelli during the COVID-19 pandemic in 2020.
Scotland team:
15-Kyle Rowe, 14-Kyle Steyn, 13-Huw Jones, 12-Sione Tuipulotu, 11-Duhan van der Merwe, 10-Finn Russell (captain), 9-Ben White; 1-Pierre Schoeman, 2-George Turner, 3-Zander Fagerson, 4-Richie Gray, 5-Scott Cummings, 6-Luke Crosbie, 7-Jamie Ritchie, 8-Matt Fagerson
Replacements: 16-Ewan Ashman, 17-Alec Hepburn, 18-Elliot Millar-Mills, 19-Sam Skinner, 20-Jack Dempsey, 21-George Horne, 22-Ben Healy, 23-Cameron Redpath.