Kinghorn, Van der Merwe dropped by Scotland for Six Nations opener
Bristol's Tom Jordan starts at full-back, in place of Kinghorn, flanked by Glasgow wings Kyle Steyn and Jamie Dobie for the match in Rome.
Van der Merwe and Kinghorn fail to even make the bench with Graham, Adam Hastings and George Horne the replacement backs.
Steyn and Dobie are two of nine Glasgow players in the starting 15 -- a reward for the team's fine form.
Franco Smith's side lead the United Rugby Championship and have defeated Toulouse and Saracens over the past month to make a perfect start in the European Champions Cup.
"Blair, Duhan and Darcy have had some terrific games for us and they're very proud playing for Scotland," said Townsend after announcing his team on Thursday. "But there is competition in that back three area.
"We feel Jamie, Kyle, and Tom deserve their starts given how well they've been playing.
'No truth' Townsend has signed Newcastle deal
Townsend was also pressed on a report in Britain's Daily Telegraph that he is to take over as Newcastle coach following the conclusion of the 2027 World Cup.
The 52-year-old former Scotland playmaker, who has coached his country since 2017, is already acting as a part-time consultant to Red Bull since they acquired the English Prem club last year.
Townsend is contracted with the Scottish Rugby Union until next year's World Cup in Australia.
"There's no truth I've signed the contract beyond the World Cup and my focus is on the Scotland team right now and hopefully up to the World Cup," added Townsend.
"It's a story that is being put out there to try to disrupt ahead of this game or next week's game against England."
Scotland lost on their last visit to Rome in 2024 and Townsend is determined not to let the optimism built by Glasgow's recent results be extinguished on the opening weekend of the championship.
"It's our most important game. When you look at the context of the Six Nations it's a lot about momentum.
"You build momentum through performances, and with three games in a row this year it's going to be massive.
"You roll on to next week pretty quickly so getting a performance and win will really help how you're going to play the rest of the tournament."
Scotland (15-1)
Tom Jordan; Kyle Steyn, Huw Jones, Sione Tuipulotu (capt), Jamie Dobie; Finn Russell, Ben White; Jack Dempsey, Rory Darge, Matt Fagerson; Grant Gilchrist, Scott Cummings; Zander Fagerson, Ewan Ashman, Pierre Schoeman
Replacements: George Turner, Nathan McBeth, Elliot Millar-Mills, Max Williamson, Gregor Brown, George Horne, Adam Hastings, Darcy Graham
Coach: Gregor Townsend (SCO)