Leicester hooker Tom Youngs will make his Test debut against Fiji on Saturday after being confirmed in one of the most inexperienced England sides of the professional era.
Youngs will take over the hooking duties from Dylan Hartley, who has been sidelined with a knee injury which threatens to keep him out of England's entire QBE autumn international series.
Ugo Monye will make his England comeback on the left wing in place of the injured Ben Foden, while Charlie Sharples deputiseS for the suspended Chris Ashton on the right wing.
Alex Goode continues at full-back while Brad Barritt and Manu Tuilagi link up in a hard-hitting centre partnership, with Toby Flood and Danny Care the half-backs.
There are a total of five changes from the 14-14 draw with South Africa in the summer, with Chris Robshaw back to captain the side after missing that Test with a broken hand.
Tom Johnson continues at blindside flanker after making his Test debut on the summer tour, while Tom Wood returns to the England fold after 14 injury-plagued months with a place on the bench.
The uncapped pair of Saracens prop Mako Vunipola and Wasps lock Joe Launchbury are primed to make their Test debuts off the bench.
Flood is the most experienced player in the England side with 50 caps. The combined total of England's starting line-up is just 215.
Flood (50), Care (33), Tom Palmer (40) and Dan Cole (31) account for 154 of those caps between them. Eight of England's starting line-up count their caps in single figures. Youngs is uncapped.
To put that in context, when England fielded three debutants in their starting line-up against Scotland it was still a more experienced side than this one, with a combined total of 236 caps.
"Congratulations to Tom Youngs, who has made a great transition from centre to hooker in a short period and deserves his chance, as do Joe Launchbury and Mako Vunipola, who we are pleased to be able to include in the squad," said head coach Stuart Lancaster.
The last time England played a Test at Twickenham, they completed a resounding victory over Ireland to finish second in the RBS 6 Nations.
This autumn, England return home to face Fiji, Australia, South Africa and New Zealand on successive Saturdays knowing they must retain fourth place in the rankings to be top seeds at the 2015 Rugby World Cup.
The pool draw for the tournament takes place in London on December 4.
Lancaster said: "This QBE International series will be a real marker of where we are as a squad. We are playing four back to back matches in four weeks against the top teams in the world and we are confident we can rise to the challenge. The foundations are in place, now it's time for us to execute and deliver.
"Fiji is a good first Test for us and we can't wait to play back at Twickenham. The atmosphere against Ireland back in March was superb and you can't underestimate what it means to the players to have 82,000 people and the nation behind them."
Tom and Ben Youngs, who is on the bench as back-up for Care, could become the first brothers to play together for England since Delon and Steffon Armitage in 2009.
Tom Youngs' selection may have been predicated by Hartley's injury but it completes a remarkable rise for the 25-year-old, who has made just seven Aviva Premiership starts at hooker.
Youngs played England age-group rugby as a hard-hitting centre and he was on the fringes of the Leicester side when Tigers director of rugby Heyneke Meyer suggested he should become a hooker.
The conversation occurred after Youngs had been involved in a mass brawl while captaining the Leicester second team against Saracens.
That was three years ago. Youngs went out on loan to Nottingham to learn his new trade and caught the eye of England's forwards coach Graham Rowntree.
Youngs toured with England in the summer, playing two midweek matches, before returning to Leicester and establishing himself as the Tigers' first-choice hooker.
There are still question marks over his throwing but Rowntree is convinced Youngs has the makings of a top-class international player.
"You can't expect Tom to be the finished article from day one but the signs are he is going to be a very, very good player going forward," Rowntree said.
"You have to learn at the coal face and he is learning quickly.
"He has not had it all his own way in terms of the line-out.
"What impresses me is how he has recovered from setbacks within games. He is a strong character and will get stronger and stronger.
"You have to be able to throw and scrummage under pressure. The things he brings outside that, the real dynamic stuff, sets him ahead of other people. I have every confidence in him."
England team for the QBE international against Fiji at Twickenham on Saturday, November 10 (kick-off 2.30pm):
A Goode (Saracens); C Sharples (Gloucester), M Tuilagi (Leicester), B Barritt (Saracens), U Monye (Harlequins); T Flood (Leicester), D Care (Harlequins); J Marler (Harlequins), T Youngs (Leicester), D Cole (Leicester), T Palmer (Wasps), G Parling (Leicester), T Johnson (Exeter), C Robshaw (Harlequins, capt), T Waldrom (Leicester).
Replacements: D Paice (London Irish), D Wilson (Bath), M Vunipola (Saracens), J Launchbury (Wasps), T Wood (Northampton), B Youngs (Leicester), O Farrell (Saracens), M Brown (Harlequins).