Flood is no stranger to the No 12 shirt, having finished the 2007 World Cup final in that position and played there throughout the 2008 6 Nations. The other changes see Tom Plamer take over from Courtney Lawes in the second row, Nick Easter get the nod over James Haskell at No 8 and Mark Cueto return for the suspended Delon Armitage.
"It's an exciting combination for us as it gives us Toby's kicking and passing game. He's a pretty experienced Test player now and he's been playing well," said England team manager Martin Johnson.
England will be favourites to beat France and keep alive their hopes of reaching a third successive World Cup final, although Johnson doesn't believe the French are in quite the same state of disarray as many people belive..
"They've got pride in their team and country and they'll come and play. They are very dangerous, no more so than when they're written off.
"We've got to get tempo into our game, which we didn't do against Scotland. We let them take the initiative early on and we were 12-3 down.
"We need to be better in the first 20 minutes and give ourselves a platform to work from, instead of fighting back from."
England: Ben Foden (Northampton Saints); Chris Ashton (Northampton Saints), Manu Tuilagi (Leicester Tigers), Toby Flood (Leicester Tigers), Mark Cueto (Sale Sharks); Jonny Wilkinson (Toulon), Ben Youngs (Leicester Tigers); Matt Stevens (Saracens), Steve Thompson (London Wasps), Dan Cole (Leicester Tigers), Louis Deacon (Leicester Tigers), Tom Palmer (Stade Francais), Tom Croft (Leicester Tigers), Lewis Moody (Bath, Captain), Nick Easter (Harlequins)
Replacements: Dylan Hartley (Northampton Saints), Alex Corbisiero (London Irish), Courtney Lawes (Northampton Saints), Simon Shaw (Unattached), James Haskell (Ricoh Black Rams), Richard Wigglesworth (Saracens), Matt Banahan (Bath)