The International Rugby Board has confirmed that the North v South clash of the rugby hemispheres will take place at Twickenham on 30 November.
The Millennium Stadium bid for the game when the fixture was initially put out to tender, but the IRB have now opted to go to London for the inaugural fixture.
"The match was put out to tender, and the WRU duly submitted a bid. It was never at any stage formally agreed that it would be in Cardiff, and we're obviously disappointed to have missed out on this occasion," said WRU media manager Lyn Davies.
South Africa's Andre Watson has already been named as the referee for the game and the IRB will shortly announce a match sponsor and TV broadcaster.
Set to become a biennial event in the rugby calendar, the proceeds will go towards the development of rugby in the smaller playing countries around the globe.
IRB chief executive Mike Miller claims there is "tremendous enthusiasm" for the game.
The IRB will also hold their Annual Awards ceremony in London on the same day as the game.
Wales Under 20 travel to Newcastle on Friday to face England at Kingston Park. With the likes of Jack Dixon and Ashley Evans returning to the squad, it's arguably the strongest side head coach Byron Hayward has put out in the tournament so far. WRU TV previews the game with Defence Coach Richard Hodges and captain Steffan Hughes.
Wales head coach Warren Gatland gives an exclusive interview to WRU TV after naming his side to face England in the RBS 6 Nations at Twickenham on Sunday. Gatland has recalled British & Irish Lions duo Jonathan Davies and Alun Wyn Jones to his side while Rhys Webb retains his place at scrum half.
Scrum half Rhys Webb and lock Jake Ball both made their first Wales starts in last Friday's win over France at the Millennium Stadium. They talk exclusively to WRU TV's Luke Broadley about their experiences of the day.
Wales Women's Head Coach Rhys Edwards has made three changes to his side to face France at Aberavon on Sunday, where he expects his side to be given a tough time against one of the best teams in the world.