Francesca McGhie will make her debut on the left wing when Scotland open away to defending champions England in the Six Nations.
Coreen Grant has been given her first start on the opposite flank.
Meryl Smith and Emma Orr form the centre partnership, with just 10 caps between them.
Scotland finished bottom in last year's competition and are on a run of nine successive defeats as they take on the side ranked number one in the world.
England have scored more than 50 points against the Scots in their past four meetings.
Centre Beth Blacklock, who was a national academy representative with England, is in line to make her debut off the bench.
Full-back Chloe Rollie and hooker Lana Skeldon are the only players with more than a half century of caps in Bryan Easson's squad.
'Best tournament in the world'
"We're really excited to play against the best team in the world at a sold-out stadium in Newcastle," said the head coach. "It's the best tournament in the world.
"We've got a lot of new young faces and lot of experience still in here.
"Fran has been scoring tries for fun for The Thistles [Scotland development side]. She's powerful and she has that youthful exuberance as well.
"We've been keeping an eye on Beth for a while. She brings a good go-forward in terms of a 12 and a great skill-set with her running and kicking."
Scotland: Chloe Rollie, Coreen Grant, Emma Orr, Meryl Smith, Francesca McGhie, Helen Nelson, Caity Mattinson; Leah Bartlett, Lana Skeldon, Christine Belisle, Lyndsay O'Donnell, Louise McMillan, Rachel Malcolm, Rachel McLachlan, Evie Gallagher.
Replacements: Jodie Rettie, Anne Young, Elliann Clarke, Eva Donaldson, Eilidh Sinclair, Mairi McDonald, Beth Blacklock, Liz Musgrove.