Former sevens player Helena Rowland will make her first XVs start for England at fly-half as head coach Simon Middleton gives his younger players a chance to impress against France.
Katy Daley-Mclean drops out of the matchday 23 and captain Sarah Hunter remains absent with a hamstring injury.
Zoe Harrison starts at 12, with stand-in captain Emily Scarratt at 13.
Back-to-back Grand Slam champions England face France twice this autumn - with both matches live on BBC Two.
The Red Roses were supposed to spend the autumn in New Zealand and Australia preparing for the 2021 World Cup but changed plans because of the pandemic.
They now play their closest Six Nations rivals, who they beat 19-13 in the opening match of the 2020 championship.
And Middleton is glad it gives players like 21-year-old Rowland, who earned her first XVs cap when she came off the bench in the final Six Nations game against Italy, the chance to face challenging opponents away from home.
"We see this fixture as a big opportunity for some of our younger players to play away in France, which is always one of our toughest games," he said.
"Given our two 2021 Six Nations games against France and Italy are both at home, this is a big opportunity to compete against top quality opposition away from home ahead of next year's World Cup.
"Helena Rowland has really impressed since her return to XVs with Loughborough and deserves her chance. We're really looking forward to seeing her link up with Zoe [Harrison].
"We know what Katy Daley-Mclean can do on the big stage and the presence she brings and see this as an opportunity for others."
Centre Amber Reed, who helped England beat Italy two weeks ago, misses out because of an ankle injury while scrum-half Natasha Hunt is continuing return to play protocols after testing positive for coronavirus.
Alex Matthews, who also joined Middleton's team after England sevens' funding was cut, starts at blind-side flanker and Ellie Kildunne is at full-back.
With prop Sarah Bern injured in her Premier 15s game last weekend, Shaunagh Brown starts in the front row and Harlequins team-mate Amy Cokayne joins her at hooker.
World Cup-winning prop Laura Keates is set to earn her first cap since March 2017 off the bench, while 18-year-old lock Morwenna Talling is also among the replacements.
There is no obvious replacement fly-half, with wing Kelly Smith and back Megan Jones joining scrum-half Claudia MacDonald on the bench.
"It is all set to be a typical ding-dong France game with maybe one score in it," Middleton added.
"We have beaten them the last five times we have played them but only one game has been by more than one or two scores. England against France is always a great game."
England games to be shown on BBC Two
Saturday's game in Grenoble will be shown live on BBC Two and BBC iPlayer, as will the return fixture at Twickenham on 21 November.
RFU head of women's performance Nicky Ponsford said: "We are delighted that the BBC will be showing our two autumn matches.
"We have two strong teams competing and expect two tough matches. We know how important visibility is in growing the women's game and will be aiming to put on a show for everyone watching from home."
Line-up
England: Kildunne; Breach, Scarratt (capt), Harrison, Dow; Rowland, Riley; Cornborough, Cokayne, Brown, Ward (vice-capt), Cleall, Matthews, Packer, Beckett.
Replacements: Davies, Harper, Keates, Talling, Millar-Mills, MacDonald, Smith, Jones.