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Gareth Southgate’s men know that avoiding defeat would seem them through to the knockout stages while a victory would secure top spot.
For Robert Page’s side things look infinitely tougher with the Welsh knowing they must record a big win over their neighbours to have any hopes of progressing.
Wales vs England latest odds
The Three Lions have won the last six meetings with Wales and bet365 offer them at just 4/9 (1.44) to record another triumph.
Wales for their part can be backed at 7/1 (8.00) for what would be a historic success, with the draw available at 7/2 (4.50).
Wales vs England first goal scorer odds
Harry Kane is yet to score in the tournament, but the Tottenham forward remains the shortest priced player to break the deadlock at 11/4 (3.75).
Raheem Sterling is priced at 9/2 (5.50) while Bukayo Saka is available at 8/1 (9.00).
For Wales, Gareth Bale the scorer of their only goal in the competition so far is available at 9/1 (10.00) ahead of Bournemouth forward Kieffer Moore at 12/1 (13.00).
Wales vs England preview
While both goals in their 2-0 defeat to Iran came in injury time, Wales were comfortably outplayed by the number one ranked Asian team.
The Iranians were able to exploit big gaps in the Welsh midfield, and England have more than enough quality in the centre of the park to be able to dictate play on Tuesday night.
The last meeting between these sides came two years ago with England winning a friendly by a comfortable 3-0 score line and there is every chance that a similar result could be on the cards against their limited local rivals.
Wales vs England tips and predictions
The Three Lions are priced at 4/6 (1.65) to win with a -1 handicap and that price should be big enough to attract attention, while they are offered at 5/4 (2.25) to score in each half which looks like an attractive option.
Odds correct at the time of writing. Please gamble responsibly.