Props Will Hurd and Nathan McBeth, and lock Ewan Johnson, will make their first Scotland starts against Chile on Saturday.
Gregor Townsend has made 10 changes to his starting line-up after last weekend’s 42-7 victory over USA, which followed a 73-12 thrashing of Canada.
Edinburgh fly-half Ben Healy makes his first outing of the four-Test tour, while scrum-half Jamie Dobie is again deployed on the wing.
Sale Sharks pair Gus Warr and Arron Reed impressed on debut in Ottawa and return to the backline, joining Glasgow Warriors skipper Kyle Steyn, full-back Kyle Rowe and co-captain Sione Tuipulotu.
Fellow co-skipper Jamie Ritchie retains his place after earning his 50th cap in Washington DC. Bath’s Josh Bayliss and Warrior Gregor Brown complete the back-row.
South Africa-born Dylan Richardson starred against the Canadians, carrying for more than 150m, and wears the number two jersey.
Patrick Harrison, 22, will deputise for Richardson from the bench and is set to win his first cap.
Hurd, McBeth and Johnson all made debuts in the tour curtain-raiser.
Leicester tight-head Hurd, 25, was selected for the wider Six Nations squad earlier this year before a foot injury curtailed his involvement.
Loose-head McBeth, 26, who represented South Africa Under-20s, recently helped Glasgow claim the URC title against the Bulls in the land of his birth.
Johnson, a 6ft 8in second row, was raised in France, where he has played all of his club rugby for Racing 92, Vannes and Oyonnax.
Chile participated at their first Rugby World Cup last year and began their July programme with home victories over Hong Kong China and Belgium.
Los Condores hosted Scotland A in a friendly match two years ago, with the visitors prevailing 45-5.
Scotland complete their Americas tour against Uruguay on Saturday, 27 July.
Scotland: Rowe; Dobie, Steyn, Tuipulotu (cc), Reed, Healy, Warr; McBeth, Richardson, Hurd, Craig, Johnson, Brown, Ritchie (cc), Bayliss.
Replacements: Harrison, Schoeman, Sebastian, Williamson, Darge, Hastings, McDowall, Currie.