Captain Owen Farrell will make his return from suspension at fly-half with Marcus Smith starting at full-back as England face Chile.
Amongst the dozen changes England have made, Elliot Daly shifts to outside centre to form a new partnership with Ollie Lawrence, while Henry Arundell fills Daly's shirt on the left-wing and Max Malins comes in on the right.
Danny Care completes an all-new backline formation, starting at scrum-half, with Kyle Sinckler and Lewis Ludlam the only forwards continuing from the win against Japan last Sunday.
Ludlam moves to the blindside with Billy Vunipola at number eight, as Jack Willis makes his first appearance on the openside. David Ribbans and George Martin come together in a new second row partnership, and Bevan Rodd and Theo Dan join Sinckler in the front row.
Jack Walker will look to make his first appearance of the tournament, with Harlequins teammates Joe Marler and Joe Marchant – off to Stade Francais next season – for company amongst the substitutes.
Will Stuart remains on the bench with Ben Youngs, alongside Youngs' former fellow Leicester half-back George Ford as well as another Tiger in the form of Ollie Chessum, and Ben Earl looking to stay in form.
With Farrell hoping to gain some, the 107-capped fly-half is relishing the chance to finally get in the action.
“I wouldn't describe myself as a good watcher,” he said “I feel involved, I feel like I'm out there at times.
“I feel every emotion that goes with it, sometimes even more than I would if I was playing. I wouldn't describe myself as the best in the stands!
“I wouldn't say I am unbelievably loud, it's just more the emotion of the game. I feel like I go through it all time.
“I'm massively excited to be back. I've been looking forward to getting to the World Cup and it's been tough-ish not playing.
“It's been brilliant to see how well the lads have been doing on the pitch and I'm desperate to be a part of it.”
Steve Borthwick has dramatically relieved pressure on his position after two wins, and is excited to have his captain back.
After praising Farrell's understudy Ford, who has scored 41 points in the first two rounds, he hinted at the possibility of having the pair playing together.
“George Ford has been in superb form,” said Borthwick, who confirmed that Farrell remains the squad's captain despite Lawes performing well in the role against Argentina and Japan.
“Will we see George Ford and Owen Farrell at 10 and 12? I think that could happen at some point in the game,” Borthwick said.
“They've been a great partnership in the past. They have been working together in training.
“They have known each other for a very, very long time and you have seen the way they can work together. There's a great synergy between them.”
Borthwick also had praise for two youngsters in his new back three trio, insisting that Smith playing at full-back was going to work despite the Harlequins fly-half making his first professional start in that position.
“Everyone knows Marcus' ability with ball in hand. Everyone knows he's got a great tactical kicking game,” Borthwick said.
“Having that ball in space at 15 gives him even more time to find opportunities and find more space.
“What we are seeing from him is that his ability under the high ball is very good and he's a really tough, brave defender.
“You don't want your full-back to make many tackles but when they do they are usually pretty important ones. Marcus has shown himself to bring a real intensity to his defence as well.
“Having Marcus as an option there is a great strength for us. Given the way he has come on to the field and played in the position, he deserves this opportunity.”
Henry Arundell, the youngest player in the England squad looking to make his first World Cup appearance, was also backed by the boss, as Borthwick made special mention to his ability to make breaks and play with his head up.
“Henry has got a special talent and ability to beat people. Henry is a very instinctive player so I talk about backing his instincts,” Borthwick added.
“If he makes a decision to go, then go. Beat people. It's what he does so very, very well. He has added other dimensions to his game.
“His defence has really, really stepped forward, his high ball has really improved. He has been working exceptionally hard on it.
“His point of difference is his ability to beat people, so I encourage him to go and beat people.”
England: Smith; Arundell, Daly, Lawrence, Malins; Farrell, Care; Rodd, Dan, Sinckler, Ribbans, Martin, Ludlam, Willis, Vunipola
Replacements: Walker, Marler, Stuart, Chessum, Earl, Youngs, Ford, Marchant
Chile: Urroz; Game, D Saavedra, Garafulic, Velarde; Fernandez, B Videla; Lues, Bohme, Dittus, C Saavedra, Eissmann, Sigren (c), Silva, Escobar
Replacements: Dussaillant, Lastra, Gurruchaga, Huete, Orchard, Martinez, Carvallo, Ayarza
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