Wales have not won at Twickenham in the Six Nations since 2012, but England head coach Eddie Jones and his men will be under no illusion about the size of challenge that awaits them this weekend.
Victory for England will secure the Triple Crown and keep alive their hopes of a third title in five years, while Wales will be motivated to avoid a third consecutive Six Nations defeat under new coach Wayne Pivac.
Former England fly-half Paul Grayson and ex-Wales fly-half James Hook look at four key battles that could decide the match.
Fly-half - George Ford v Dan Biggar
Paul Grayson: "This will be a proper head-to-head. George Ford is a natural flat-to-the-line 10 who manipulates defenders. Sometimes he stops doing that with Owen Farrell at 12 when England look to move the ball through another set of hands, but they play better when Ford takes the ball to the line.
"Dan Biggar is less natural at that but he has added it to his game since he has moved to Northampton. What he has is a ferocious competitive streak and he is a Test match animal that is absolutely desperate to win. His strength is his relentless pursuit of excellence, but it can spill over sometimes and he gets animated if things aren't going his way."
James Hook: "They are different 10s. Ford is more attacking and he takes the ball to the gain line and engages defences much more. Biggar is more of a threat aerially and his winning mentality is right up there. He is very confident in his own ability and he drives the team on."
Wing - Anthony Watson v Liam Williams
Grayson: "Both players are important in the team and each starting XV would always have their names in it if they are fit. Anthony Watson coming back to Test match level instantly after the Achilles injury is amazing. Fully fit, he is a dead cert to start for England and Liam Williams is the same for Wales - he has emerged as a genuine Test player at full-back or on the wing.
"I think they're slightly different in the way they play. Both are aerially very strong, Watson just edges it on pace but Williams is more physical. Both teams will be looking to get the ball to them and they are exceptionally good rugby players.
"Pivac is under some pressure for results so he has gone for his most experienced side. Off the back of the Gatland era there is external pressure from the Welsh public, and having lost at home to France, it will be tough to win at Twickenham."
Hook: "It's a huge battle. Watson has magical feet and Williams has been picked as part of a fantastic back three to defuse those high kicks from England. It's a tried and tested back three."
Second row - Maro Itoje v Alun Wyn Jones
Grayson: "That is a battle of the generations, you can see Maro Itoje being around for as long as Alun Wyn Jones, who is a phenomenal performer. His leadership and his physicality is immense. Itoje is showing all the same traits. He got to the top very quickly and he has had a few distractions with Saracens but he is back to his best form, and when he is playing well he is as influential in his pack as Wyn Jones is in his.
"He is a good line-out operator and he is a great spoiler. He has a sense of the big occasion and he comes up with the big play when he needs it. It is a genuine Test battle between a guy that is coming to the end and a youngster who has already scaled the heights who could become a legend."
Hook: "Always a tough battle. Itoje grows every game and Wyn Jones keeps delivering. They are two winners. England are strong up front so you know which way they will go but just having Wyn Jones around, with his mentality and presence, is so important for Wales. When he is not playing you notice it."
Number eight - Tom Curry v Josh Navidi
Grayson: "Taulupe Faletau, coming back from injury, has played OK but he hasn't had a lot of rugby. Josh Navidi has been excellent for Wales over the last year and his selection is not surprising. Eddie Jones has decided Tom Curry could be a better number eight than he is an openside flanker, a position which he is probably in the top three or four in the world at the moment.
"He has grown so much physically and in terms of his performances at international level. He did not have his best outing for the first time at eight in France and he made some rookie mistakes but he is a quick learner. England probably have a bit more physicality than Wales, who want to play a bit more on the edges under Pivac and you need that bit of pace to get there. Navidi suits that style and Curry is a powered-up flanker who is learning number eight skills."
Hook: "It's a big call by Wales. Navidi gives 100% and he is a great ball carrier. He is a different player to Faletau, who is more of a natural number eight, but Navidi carries well and he is good on the floor. Curry is a great prospect. Jones is not afraid to put people in and he has been rewarded by his form for Sale."
Paul Grayson and James Hook were speaking to BBC Sport's Mantej Mann
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