Owen Farrell has been named at fly-half for England's autumn series opener against South Africa at Twickenham on Saturday.
The Saracens playmaker starts in the position for only the third time in the Eddie Jones era, forcing George Ford to settle for a place among the replacements.
In a gamble by Jones, Ben Te'o has been picked at inside centre despite being limited to only 28 minutes of rugby since May due to thigh and calf injuries.
The inclusion of Te'o means Manu Tuilagi is confined to a bench a role where he will win his first cap since 2016 as an impact substitute.
Chris Ashton has failed to make the matchday 23 altogether with Jonny May and Jack Nowell preferred on the wings.
Completing the backline is Henry Slade's inclusion at outside centre, the position he filled throughout the 2-1 series defeat by the Springboks in June.
Filling the void left by an injury crisis at number eight is Mark Wilson, who will be winning his fifth cap in the absence of Billy Vunipola and Nathan Hughes.
Brad Shields returns at blindside flanker and Tom Curry continues in the number seven jersey in a back row containing a mere 10 caps.
Alec Hepburn has held off the challenge of Exeter club mate Ben Moon to start at loosehead prop and the uncapped Zach Mercer features on the bench.
Dylan Hartley, co-captain alongside Farrell, has more caps than the rest of the pack put together having made 93 international appearances.
England return from their week-long Portugal training camp on Thursday night to begin final preparations ahead of the first of four Quilter Internationals at Twickenham this month.
"We've become very well organised in our set-piece and have done a lot of good work in Portugal over the last week," Jones said.
"We have put in a new defence system and our attack looks more organised than it was on the South Africa tour.
"Against South Africa you have got the physical battle up front and then you have to be tactically smart in how you attack against them.
"We need to find ways to gain momentum, then once we find momentum, convert that to points. We are really excited to be back at Twickenham Stadium. It's been a long time and we can't wait to play in front of 82,000 fans."
— England Rugby (@EnglandRugby) November 1, 2018
England team to play South Africa
Forwards: 1 Alec Hepburn (Exeter Chiefs), 2 Dylan Hartley (CO-CAPTAIN, Northampton Saints), 3 Kyle Sinckler (Harlequins), 4 Maro Itoje (Saracens), 5 George Kruis (Saracens), 6 Brad Shields (Wasps), 7 Tom Curry (Sale Sharks) , 8 Mark Wilson (Newcastle Falcons)
Backs: 9 Ben Youngs (Leicester Tigers), 10 Owen Farrell (CO-CAPTAIN, Saracens), 11 Jonny May (Leicester Tigers), 12 Ben Te’o (Worcester Warriors), 13 Henry Slade (Exeter Chiefs), 14 Jack Nowell (Exeter Chiefs), 15 Elliot Daly (Wasps)
Replacements: 16 Jamie George (Saracens), 17 Ben Moon (Exeter Chiefs)*, 18 Harry Williams (Exeter Chiefs), 19 Charlie Ewels (Bath Rugby), 20 Zach Mercer (Bath Rugby)*, 21 Danny Care (Harlequins), 22 George Ford (Leicester Tigers), 23 Manu Tuilagi (Leicester Tigers)
* Denotes uncapped player