The Bath back will know he is under pressure to deliver as he starts his first Test match in a year.
Head coach Andy Robinson has reacted to last weeks 11-9 defeat by Wales by making five personnel changes and two positional switches for the clash with the French.
Newcastle's teenage midfield prodigy Mathew Tait, scrum-half Matt Dawson, injured prop Julian White and back-row pair Chris Jones and Andy Hazell all miss out following arguably the worst England performance in recent years.
Big-kicking Barkley will line up at inside centre Jamie Noon moves across to wear Tait's number 13 jersey with Harry Ellis replacing Dawson.
Phil Vickery takes over from White, Lewis Moody ousts Hazell and Martin Corry lines up at number eight, meaning that Joe Worsley goes to blindside flanker.
Vickery, plagued by back problems last year, makes a first England appearance in more than 10 months due to White being sidelined and Ellis is handed a full Test debut.
France coach Bernard Laporte has warned his side to be wary of wounded English pride.
The French were far from impressive in their opener in Paris where they were pushed all the way by Scotland before snatching a 16-9 victory.
Laporte has made five changes to the side who struggled to beat the Scots for Sunday's clash.
Perpignan prop Nicolas Mas, back in the fold for the first time since June 2003, replaces shoulder-injury victim Pieter de Villiers, while Sale hooker Sebastien Bruno will start for the first time as a replacement for the out-of-sorts William Servat.
Flanker Serge Betsen is named in the starting line-up after shaking off a right thigh injury, but he could still miss out should he be banned for an incident that occurred during Biarritz's European Cup clash with Wasps last month.
The other two changes see scrum-half Dimitri Yachvili and winger Jimmy Marlu brought into the side.
Yachvili will start instead of Pierre Mignoni and he will be the kicker at Twickenham, while Marlu replaces Aurelien Rougerie who sustained a facial injury during the Scotland match.
John Kirwan has warned Wales they will be entering the 'Colosseum' of Italian rugby when they run out at the Stadio Flaminio this weekend.
Kirwan said: "It was fantastic to see the way our fans supported us against Ireland and it will be the same atmosphere again."
Italy enter their second championship clash in high spirits following an opening defeat which came in hugely encouraging circumstances 28-17 against favourites Ireland.
It therefore came as little surprise when Kirwan named an unchanged side yesterday.
Wales are due to fly out to Rome today with only one injury concern after lock Brent Cockbain was given the all-clear following a slight neck problem.
Flanker Martyn Williams has been declared fit although he has not been in contact training until yesterday.
Scotland coach Matt Williams wants his players to put the disappointment of the RBS 6 Nations opener behind them as he prepares to name his team for the game against Ireland on Saturday.
The Scots had been looking for a huge improvement in fortunes against France after a disappointing November Test series but were hit by Damien Traille's try and lost 16-9.
Williams must now decide whether to keep faith with the XV who played so admirably against the French when Ireland arrive at Murrayfield.
But the former Leinster coach must wait on the fitness of two Paris heroes.
Wing Simon Danielli has a bruised thigh while back row forward Jason White is suffering from a bruised bicep although neither is expected to miss out.
However, the presence of Lions coach Clive Woodward at a Murrayfield training session on Tuesday will have encouraged many players ahead of the Ireland match.
ENGLAND v France,. Twickenham, Sunday, 3pm: J Robinson (Sale, capt); M Cueto (Sale), J Noon (Newcastle), O Barkley (Bath), J Lewsey (Wasps); C Hodgson (Sale), H Ellis (Leicester); G Rowntree (Leicester), S Thompson (Northampton), P Vickery (Gloucester), D Grewcock (Bath), B Kay (Leicester), J Worsley (Wasps) L Moody (Leicester), M Corry (Leicester).
FRANCE: P Elhorga (Agen); J Marlu (Biarritz), B Liebenberg (Stade Francais), D Traille (Biarritz), C Dominici (Stade Francais); Y Delaigue (Castres), D Yachvili (Biarritz); S Marconnet (Stade Francais), S Bruno (Sale Sharks), N Mas (Perpignan), F Pelous (Toulouse, captain), J Thion (Biarritz), S Betsen (Biarritz), J Bonnaire (Bourgoin), S Chabal (Sale Sharks).