The two sides meet at the Armthorpe Road venue on Friday evening (7pm).
Here we take you through everything you need to know about the fixture…
England were the inaugural winners in 2008 and have gone on to be the tournament's most successful team, winning seven titles.
They won the Grand Slam last year.
Former Sale Sharks, Leeds Tykes, Saracens and Northampton scrum-half Alan Dickens is head coach, assisted by Alex Codling and James Tirrell.
The 2022 campaign
England won their opening game 41-24 in Scotland.
However, their hopes of winning successive back-to-back Grand Slams are over after losing to Italy for the first time in round two.
The Italians recorded a historic 6-0 win in Treviso.
How it stands
England are third in the table, behind leaders Ireland and France.
Ireland are the only side to have won two out of two, beating Wales 53-5 and France 17-16.
Wales come into this game on the back of a 26-13 win over Scotland.
England were comfortable 45-3 winners when these sides met at Cardiff Arms Park last year.
However, Wales prevailed 23-22 in 2020 and also won by a single point, 11-10, in 2019.
Ones to watch
Lucas Brooke, son of All Black Zinzan Brooke, is in the England squad.
Ethan Grayson, son of England fly-half Paul Grayson, is another player to keep an eye on.
Other squad members include Robin Hardwick, son of England prop Rob Hardwick and Iwan Stephens, son of Wales international Colin Stephens.
Eye on the opposition
Wales’ only points against Ireland came courtesy of a late consolation try by winger Oli Andrew.
In their last outing against Scotland, Wales overcame a 0-7 half time score to finish 26-13 winners.
Tries by captain and back row Alex Mann, centre Joe Hawkins and winger Harri Houston turned the tide before a last-gasp score from replacement back row Morgan Morse secured the bonus point.
What they said...
“It is a great honour to host the age-grade side for their game against Wales in the 2022 U20 Six Nations.
"This will be a great event, not just for our club, but for the town and local area.
"It is an acknowledgement of the great facilities we have at Castle Park, and we are thrilled to be able to help promote the U20s.”
How to watch
Tickets are available to buy at www.drfc.co.uk. The match will be streamed live on BBC iPlayer.