Barkley - who missed the Springboks game due to a hip problem - is also back, lining up at inside-centre instead of Andy Farrell, who drops to the bench.
As expected, England head coach Brian Ashton has made sweeping changes following his team's record 36-0 World Cup loss to South Africa.
Injured Jason Robinson, fly-half Mike Catt, scrum-half Shaun Perry and flanker Tom Rees all fail to make the matchday 22 following the Springboks debacle, while Jamie Noon has returned home for further treatment on a tournament-ending knee injury.
And Lawrence Dallaglio has also failed to force his way in, with Ashton retaining Harlequins number eight Nick Easter in the back row alongside skipper Martin Corry and Wasps' Joe Worsley.
Elsewhere in the pack, Leicester hooker George Chuter is preferred to Mark Regan for his World Cup debut.
But Ashton's major surgery has taken place behind the scrum, where only Wasps wing Paul Sackey remains in his original starting position from the South Africa game last Friday.
Josh Lewsey is moved from wing to full-back instead of hamstring victim Robinson, with Mark Cueto featuring in the Number 14 shirt.
Barkley and Mathew Tait form a new centre partnership, while Wilkinson replaces Catt and Harlequins scrum-half Andy Gomarsall ousts Shaun Perry.
Perry was substituted at half-time following a miserable opening 40 minutes against South Africa, and 2003 World Cup winner Gomarsall now has a clear chance to stake his claim for the rest of this tournament.
Much will be expected of Wilkinson to get England back on a winning track after their shambolic effort at the hands of South Africa.
England must beat Samoa to keep themselves in the qualifying picture from Pool A, although their appointment with Tonga in Paris on Friday week will still effectively be an eliminator for the quarter finals.
Provided England beat Samoa and Tonga, their likely opponents in the last eight will be Australia, but Ashton can only concentrate on the next 10 days which will make or break England's World Cup campaign.