Short of centres after first-choice pairing Brad Barritt and Manu Tuilagi were injured almost before the season began and then Joel Tomkins followed them onto the treatment table, Lancaster has turned to Luther Burrell to partner Billy Twelvetrees.
The Northampton centre - a 12 for his club but playing at 13 for his country - arguably could have forced his way in on merit such has been his form this season in the Premiership.
And there is no question that uncapped Exeter Chiefs wing Jack Nowell has done just that - the 20-year-old will line up on the right wing with Jonny May, who boasts a single cap, on the opposite flank.
The inclusion of the emerging flyers means there is no place in the XV to tackle France for Chris Ashton but Lancaster believes the time was right to roll the dice.
"I've never been afraid of giving people opportunities - this time two years ago I selected seven players with no caps for Scotland away," he said.
"There is a balance to strike, but I've always been reasonably confident to pick inexperienced players if I feel they're ready.
"For me it's exciting to give young players opportunities, particularly if they've been performing well and showing it consistently at their clubs.
"At some point you have to make the step. There will be some people with less experience in the France game."
Lancaster's changes mean his backline boasts just 91 caps between them while the England coach has also opted to recall Danny Care, dropping Lee Dickson to the bench and leaving out Ben Youngs entirely.
"Competition at scrum-half has been particularly tight and Danny Care's form leading into the Six Nations has been excellent and he merits his inclusion," said Lancaster.
"Ben Youngs misses out this time but he is a quality player and I am sure he will respond in the same way Danny did at the start of the year."
Yet England are not alone in blooding new talent this weekend with France coach Philippe Saint-Andre, more by circumstance than design, handing fly-half Jules Plisson his debut.
The 22-year-old steps in after an injury to Remi Tales deprived Saint-Andre of his preferred playmaker.
Inspirational captain Thierry Dusautoir has been ruled out for the whole tournament with Pascal Pape taking over as leader but Saint-Andre has faith in his remodelled team.
"Jules has had a lot of playing time with Stade, who are the leaders of the Top 14," he said.
"They put a lot of trust in their young players which is great for us.
"We made Remi Tales the starter in the summer and we wanted to keep him for a sixth consecutive start.
"But injuries have decided otherwise and Jules is ready and focused.
"We do not have any worries about picking Plisson and (Jean Marc) Doussain to take on England."