Holly Aitchison will win her 50th England cap when she starts at fly-half in the Red Roses' WXV opener against Australia on Saturday in Manchester.
Aitchison, 28, started two of England's wins en route to their Six Nations Grand Slam earlier this year, but has been unable to supplant Zoe Harrison as head coach John Mitchell's pick at 10 for the biggest matches.
Aitchison is one of five changes to the England team that beat France in Bordeaux last time out.
Scrum-half Natasha Hunt makes her comeback from a knee ligament injury that has kept her out of action since the win over Ireland in April, while fellow World Cup winner Tatyana Heard makes her first Test appearance of the year after recovering from a foot injury.
May Campbell, whose five previous England appearances have come off the bench, makes her first Test start with resources stretched thin at hooker.
Amy Cokayne will miss the match through injury and Connie Powell is recovering from ankle surgery, while Lark Atkin-Davies is on maternity leave having had a daughter in June.
Their absences mean back-up hooker Bryony Field, who plays alongside Campbell at Saracens, is set to win her first senior England cap from the bench, where Hannah Botterman, who has not featured since 2025's World Cup final win, and Morwenna Talling are primed to make returns from injury.
Gloucester-Hartpury's Mia Venner, who finished joint top of last season's PWR try-scoring charts, come in on the wing.
Aitchinson, Heard and Talling all play for Sale Sharks, whose men's team host games at the CorpAcq Stadium, where Saturday's match takes place.
"I have very fond memories of the North West from my time with Sale Sharks so it's awesome to be able to take our game to this part of the country," said head coach John Mitchell, who spent two spells with the club as a player and a coach.
"Playing in a different part of the country allows us to be present in the community and keeps the game healthy. You've not only got to be visible, but if you can actually be close to your community, I think that's even better."
Unlike England's men, who are tied to Twickenham's Allianz Stadium by the commercial advantages of staging matches in an 82,000-capacity venue owned by the Rugby Football Union, the Red Roses are regularly on the road.
England will take on Canada for the first time since victory in the team's meeting in last year's Rugby World Cup final at Exeter's Sandy Park next weekend, before finishing the home leg of the WXV Global Series against New Zealand at Allianz Stadium on 26 September.
Away matches against Canada (twice) and the United States follow in October as part of the new-look event which aims to fill out the women's Test calendar away from the World Cup.
Australia have named the uncapped Amelia Whitaker on the wing. Whitaker, 20, is the niece of former Australia and Leinster scrum-half Chris Whitaker.
Elsewhere, exciting 19-year-old Caitlyn Halse, one of a clutch of Australians to have signed for Leicester for the next PWR season, is included at full-back.
England have won all eight of the teams' previous meetings, most recently prevailing 47-7 in the pool stages of last year's World Cup.
England: Kildunne; Venner, Jones, Heard, Moloney-MacDonald; Aitchison, Hunt; Carson, Campbell, Bern, Burns, Ives Campion, Burton, Kabeya, Feaunati
Replacements: Field, Botterman, Muir, Talling, Packer, Packer, Harrison, Rowland
Australia: Halse; Whitaker, Friedrichs, Moleka, Miller; Ellis, Wood; Hoy, Merlo, Pohiva, Leaney, Leonard, Tapsell, Bone, Palu Sekona
Replacements: Naden, Sikimeti, Karpani, Bemrose, Duck, Chancellor, Hinds, Smith
