The Dark Blues cruised to a 48-10 win over Canada last weekend and head coach Gregor Townsend intends to utilise his squad to full, making a host of changes against the USA.
Matt Fagerson and George Horne will make their international bows alongside their elder brothers, with back-row Fagerson joined by prop Zander and scrum-half Horne lining-up alongside inside centre Pete.
There will also be debuts for the Glasgow trio Jamie Bhatti, George Turner and Adam Hastings, as well as Edinburgh's Lewis Carmichael and Luke Hamilton.
Stuart Hogg will also captain Scotland for the first time.
"We always planned to play as much of the squad as possible on this tour, and we also deliberately picked more Edinburgh players in the first game because their season finished earlier," Townsend said.
"Now we welcome most of the Glasgow Warriors contingent into the team. On top of that there are seven players making their first starts for the country, which is really exciting, and we are looking forward to them going out and grabbing this opportunity.
"The USA have won their last six games and scored a lot of points in the process. They've beaten two teams that have already qualified for the Rugby World Cup - Uruguay and Russia - and put 60 points on both of them. They are definitely improving as a team and are playing with a lot of confidence."