In total Johnson has made four changes from the side that defeated Scotland 16-12 in the final group game, but undoubtedly the most eye-catching is the inclusion of fly-half Flood at 12 with Wilkinson retaining the No.10 shirt.
It is a combination that was used in the 2008 and 2010 RBS 6 Nations, but since then Flood has evolved into a more specialist stand-off for club and country.
But with Mike Tindall still suffering the effects of a dead leg, Johnson is adamant the former Newcastle Falcons pair can hit it off again against Les Bleus.
He said: "It's an exciting combination for us. It gives us Toby's kicking game, Toby's passing game.
"He's a pretty experienced Test player now, 40 plus caps. He's been playing well. It does give us some different things that we can do on the field when we play those guys (Flood and Wilkinson).
"It's not a gamble. You always put a lot of thought into your selections, no more so than when you're in a World Cup quarter-final.
"It's one of the options we've got. I think Mike and Manu (Tuilagi) have played well together. If we had to play Shontayne; there's always an argument to play him.
"Mike took a couple of bangs last week and hasn't really been available to us this week. That was part of the equation - Mike's injury and Toby playing very well."
The other change in the backline sees wing Mark Cueto return in place of the suspended Delon Armitage.
In the pack, James Haskell who had started all of England's group games makes way for No.8 while Courtney Lawes is replaced by Tom Palmer in the second row.
Those two start on the bench but Johnson insists both will have important roles to play.
He said: "I said in front of the team that it's a particularly hard call on James. He didn't deserve it in terms of how he's played,
"But they will have a massive influence on the game. I've said this before. The guys on the bench are normally on the field at the end.
"Everyone wants to start, we all know that, but actually your role is no less coming off the bench."
15. Ben Foden - Northampton Saints
14. Chris Ashton - Northampton Saints
13. Manusamoa Tuilagi - Leicester Tigers
12. Toby Flood - Leicester Tigers
11. Mark Cueto - Sale Sharks
10. Jonny Wilkinson - Toulon
9. Ben Youngs - Leicester Tigers
1. Matt Stevens - Saracens
2. Steve Thompson - London Wasps
3. Dan Cole - Leicester Tigers
4. Louis Deacon - Leicester Tigers
5. Tom Palmer - Stade Francais
6. Tom Croft - Leicester Tigers
7. Lewis Moody - Bath Rugby
8. Nick Easter - Harlequins
16. Dylan Hartley - Northampton Saints
17. Alex Corbisiero - London Irish
18. Courtney Lawes - Northampton Saints
19. Simon Shaw - unattached
20. James Haskell - Ricoh Black Rams
21. Richard Wigglesworth - Saracens
22. Matt Banahan - Bath Rugby