George Furbank will replace Freddie Steward at full-back, with Steward moving to the wing after playing the former role in each of England's previous four games.
The Northampton man's introduction represents one of five changes made by Eddie Jones, with Ben Youngs, Nick Isiekwe, Sam Underhill, and Will Stuart the other players to be introduced, as Tom Curry, Harry Randall, Kyle Sinckler, and the suspended Charlie Ewels all drop out.
Max Malins, meanwhile, has been dropped from the squad entirely after playing every minute of the previous four Six Nations outings, as the visitors look to salvage some pride from a disappointing campaign.
Jones, who has won three Six Nations titles since taking the England reigns in 2015, has been faced with speculation regarding his future in recent days, with the team facing the prospect of finishing fifth in consecutive Six Nations campaigns, having done so in 2021.
However, the 62-year-old, while disappointed to be out of contention for the trophy, was looking forward to seeing how his much-changed side faired against Les Blues.
"This is our strongest 23 for the game against France," he said.
"We are disappointed not to be in the contention for the trophy, but last week's effort against Ireland was full of pride, energy and tactical discipline.
"We have focused on refreshing the team this week and we are ready to empty the tank on Saturday."
Only one of the last nine Six Nations meetings between France and England has been won by the visiting team, with England prevailing 31-21 back in 2016.
England: George Furbank, Freddie Steward, Joe Marchant, Henry Slade, Jack Nowell, Marcus Smith, Ben Youngs; Ellis Genge, Jamie George, Will Stuart, Maro Itoje, Nick Isiekwe, Courtney Lawes, Sam Underhill, Sam Simmonds.
Replacements: Nic Dolly, Joe Marler, Kyle Sinckler, Ollie Chessum, Alex Dombrandt, Harry Randal, George Ford, Elliot Daly.