Glasgow Warriors flanker Rory Darge will captain Scotland for the first time as they take on Italy at Murrayfield on Saturday.
The 23-year-old only earned the first of his seven caps last year - against Wales in the Six Nations.
But he previously led the Scottish team during the Under-20 Six Nations three years ago.
Warriors centre Stafford McDowall and Leicester Tigers second row Cameron Henderson will make their debuts.
Head coach Gregor Townsend has gone for an experimental and inexperienced line-up in Scotland's first game since ending the Six Nations with a 26-14 win over the same opponents in Edinburgh in March.
Captain that day Jamie Ritchie, Darge's fellow flanker, is among regular starters who will not feature in the first of a series of games - also home and away against France and at home to Georgia - as Scotland warm up for September's World Cup finals.
In all, Townsend makes 11 changes to the side that last faced the Italians, with only full-back Ollie Smith, two other Glasgow players - wing Kyle Steyn and forward George Turner - plus Edinburgh lock Sam Skinner, retaining their places.
Experienced backs Chris Harris and Ali Price are back in the XV after losing their starting places for the Six Nations earlier this year.
Edinburgh wing Darcy Graham is back in the fold after missing the entire Six Nations through injury, while his new clubmate, Ben Healy, who won his first cap during the Six Nations, will make his first start in the number 10 jersey.
Debutants McDowall and Henderson, who was born in Hong Kong but qualifies to play for Scotland through his Scottish dad, both previously featured for national age-grade teams.
The match against Italy gives Townsend the chance to run the rule over fringe players before trimming the squad to 33 in the coming weeks for the showpiece tournament in France.
Scotland team
Ollie Smith (Glasgow Warriors), Darcy Graham (Edinburgh), Chris Harris (Gloucester), Stafford McDowall (Glasgow Warriors), Kyle Steyn (Glasgow Warriors), Ben Healy (Edinburgh), Ali Price (Glasgow Warriors); Rory Sutherland (unattached), George Turner (Glasgow Warriors), Murphy Walker (Glasgow Warriors), Sam Skinner (Edinburgh), Scott Cummings (Glasgow Warriors), Luke Crosbie (Edinburgh), Rory Darge (Glasgow Warriors), Matt Fagerson (Glasgow Warriors).
Replacements: Stuart McInally (Edinburgh), Jamie Bhatti (Glasgow Warriors), Javan Sebastian (Edinburgh), Cameron Henderson (Leicester Tigers), Josh Bayliss (Bath), Jamie Dobie (Glasgow Warriors), Blair Kinghorn (Edinburgh), Cameron Redpath (Bath).