Exeter wing Jack Nowell and Northampton centre Luther Burrell will make their England debuts in Saturday's Six Nations opener against France in Paris.
There are four changes in all from the side that lost 30-22 to New Zealand at Twickenham in November.
Gloucester winger Jonny May will win his second cap, while Harlequins scrum-half Danny Care has been recalled.
Fellow Harlequin Joe Marler retains his place at loose-head prop ahead of Saracens' Mako Vunipola.
"We can't wait for Saturday," England head coach Stuart Lancaster said. "Jack and Luther deserve their chance, as does Jonny May, who will be starting his first RBS Six Nations game."
May, 23, will play on the left wing in Paris, with Lancaster keen to give an opportunity to the squad's younger players.
"I've always believed if a player's ready and deserving an opportunity, then we need to give it to them," he said. "You've got to make a debut at some point."
Winger Nowell, 20, has yet to score a Premiership try this season but impressed in Exeter's Heineken Cup ties against Toulon last month and replaces the out of favour Chris Ashton.
Ashton, 26, was dropped from the England squad after failing to score a try in the autumn internationals against Australia, Argentina and New Zealand, but Lancaster has told the Saracens winger that he remains in his selection plans.
"My message to Chris Ashton is to keep doing what he's doing and keep working on the little things all players have to work on," he said.
"I've always played him on that right wing and now feel it's time to give someone else the opportunity. I'm sure Chris will be training well and fighting for that place against Scotland [on 8 February at Murrayfield]."
Huddersfield-born Burrell, 26, who has also played sevens for the West Indies, has been in outstanding form for Northampton at inside centre but plays one position further out on Saturday.
Care, 27, started only one Test last year, against Italy in the Six Nations, but reclaims the number nine shirt from Lee Dickson of Northampton, who moves to the bench, while Leicester's Ben Youngs has been dropped.
"Scrum-half was the most competitive position of all," Lancaster said.
"Danny Care suffered the disappointment of not being involved in the first game in the autumn. We gave him some areas to work on - his game management, his kicking game - and he's gone away and done that.
"Ben is no different. He'll come back fighting for that team spot in the Scotland game and beyond."
Lancaster has opted to keep the same pack that started against the All Blacks, but expects Leicester hooker Tom Youngs, 27, and Vunipola, 23, to feature from the bench.
"We felt the pack went well in the autumn and it's right to leave it unchanged," said Lancaster. "But we have some quality players, including two British Lions in Tom and Mako, to come on."
France have a debutant of their own, with fly-half Jules Plisson set to make his first appearance for Les Bleus on Saturday.
The England squad will travel to Paris by Eurostar train because air traffic controllers in Europe are on strike on 29-30 January.
England: Mike Brown; Jack Nowell, Luther Burrell, Billy Twelvetrees, Jonny May; Owen Farrell, Danny Care; Joe Marler, Dylan Hartley, Dan Cole, Joe Launchbury, Courtney Lawes, Tom Wood, Chris Robshaw, Billy Vunipola.
Replacements: Tom Youngs, Mako Vunipola, Henry Thomas, Dave Attwood, Ben Morgan, Lee Dickson, Brad Barritt, Alex Goode.