Red Rose boss Eddie Jones has replaced injured scrum-half Ben Youngs with Danny Care of Harlequins while Jonathan Joseph steps in for Ben Te’o in midfield.
Powerful centre Te’o drops to the bench where he is joined by Richard Wigglesworth and Jack Nowell. Sam Simmonds continues at No 8 after impressing in the convincing win over Italy.
“The team is hugely excited about playing in front of 82,000 fans at Twickenham and we’ll be well prepared and ready to go out there and beat Wales on Saturday,” said Jones.
“Danny very much deserves the honour of being the most capped England scrum-half and I am sure he’ll make the most of his opportunity on Saturday.”
England have won the last two Six Nations titles and thrashed Italy 46-15 in their first match this year.
Wales are next up, Jones opting to keep the same back-row which started in Rome.
Courtney Lawes and Chris Robshaw are on the flanks with Simmonds at the base of the scrum.
Former Ospreys flanker Sam Underhill is on the bench.
In the back division, Care and Joseph are the headline figures with George Ford and Owen Farrell continuing in their playmaker roles.
Mike Brown, Anthony Watson – who scored twice against Italy – and Jonny May will make up the home side’s back three.
Jones added: “We want to be an adaptable team and to be able to play to the conditions, referee and game as sometimes the game controls you.
“Wales will try and play a particular way but in terms of winning the game we want to make sure our set-piece is dominant and our defence is ferocious.”
On his selection of Joseph over Te’o, Jones said: “It’s a gut feeling on my behalf, Ben worked really hard to get back fit, but experience tells me sometimes in their second game back players are a little bit flat.
“JJ has been in good form in training. He’s powerful, quick and will defend well.
“He can do a job for us from the start and Ben will come on and give us power and impetus, just as he did last week.”
England XV: Mike Brown; Anthony Watson, Jonathan Joseph, Owen Farrell, Jonny May; George Ford, Danny Care; Mako Vunipola, Dylan Hartley (capt), Dan Cole, Joe Launchbury, Maro Itoje, Courtney Lawes, Chris Robshaw, Sam Simmonds
Replacements: Jamie George, Alec Hepburn, Harry Williams, George Kruis, Sam Underhill, Richard Wigglesworth, Ben Te’o, Jack Nowell
