Courtney Lawes will make his first England start at blindside flanker as one of three changes coach Stuart Lancaster has made against France.
Lawes' nine previous England starts have all been at lock but he has been pressed into back-row action in place of James Haskell, whose preparations have been disrupted by the flu.
Manu Tuilagi returns to the England midfield in place of Billy Twelvetrees, after making his comeback from an ankle injury via the bench in the 12-6 victory over Ireland.
Dylan Hartley has replaced Tom Youngs at hooker as unbeaten England tackle a French side reeling from their worst start to a championship campaign for 31 years.
Haskell, Youngs and Twelvetrees all feature on the bench.
Lancaster said: "We thought long and hard about changing a winning team which did so well against Ireland.
"But we believe that Dylan, Courtney and Manu are ready for the opportunity and allow us to vary our play, while the bench will add impact and energy as the game unfolds in the second half.
"The players are really looking forward to getting back to Twickenham.
"The atmosphere in the stadium is fantastic and hopefully the crowd can get behind us in what is sure to be a great challenge against a motivated and physical French team."
France have made eight changes to the side beaten by Wales, with Wesley Fofana returned to the midfield as part of a powerful centre combination with Mathieu Bastareaud.
Tuilagi's return sets up a seismic midfield battle with Brad Barritt, England's defensive rock, returning to his more natural position at inside centre.
All three England changes indicate an intent to be abrasive and physical against France.
Lawes has been used as a high-impact replacement so far this championship. He has played at blindside flanker for Northampton before and he will also offer England an additional lineout option.
Hartley missed the QBE autumn internationals through injury and had to content himself with a place on the bench for England's wins against Scotland and Ireland, such was Youngs' form.
But Lancaster and forwards coach Graham Rowntree have opted to recall the more experienced Hartley to combat, given the stiff examination they expect from the French pack.
Unusually, the reshuffle means England go into the game with no second row or back three cover on the bench. An injury in either department would result in a reshuffle.
Lawes would cover the second row and Tuilagi, presumably, would slot into the back field should England lose one of Alex Goode, Mike Brown or Chris Ashton during the game.
England team to play France in the Six Nations at Twickenham on Saturday, February 23 (kick-off 1700): A Goode (Saracens); C Ashton (Saracens), M Tuilagi (Leicester Tigers), B Barritt (Saracens), M Brown (Harlequins); O Farrell (Saracens), B Youngs (Leicester Tigers); J Marler (Harlequins), D Hartley (Northampton Saints), D Cole (Leicester Tigers), J Launchbury (London Wasps), G Parling (Leicester Tigers), C Lawes (Northampton Saints), C Robshaw (Harlequins, capt), T Wood (Northampton Saints).
Replacements: T Youngs (Leicester Tigers), D Wilson (Bath Rugby), M Vunipola (Saracens), J Haskell (London Wasps), T Waldrom (Leicester Tigers), D Care (Harlequins), T Flood (Leicester Tigers), B Twelvetrees (Gloucester Rugby).
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