Wales (16) 16
Pens: Halfpenny 2
Drop goal: Biggar
England (8) 21
Try: Watson, Joseph
Pens: Ford 3
England staged a stunning second half comeback to defeat Wales and avenge the harrowing defeat in Cardiff two years ago with victory in a pulsating Six Nations opener at the Millennium Stadium.
Rhys Webb's try helped the Welsh into a 10-point lead after just eight minutes as Warren Gatland's side threatened a repeat of the 30-3 win from 2013.
But Anthony Watson's first England try and Jonathan Joseph's brilliant score either side of half-time handed the away side the initiative.
Alex Cuthbert was sin-binned mid-way through the second 40 minutes and from the infringement George Ford's penalty put his side ahead, before a further three points in the final minute handed England a momentous and unlikely victory.
Defeat meanwhile for Wales leaves their hopes of claiming their third championship in four years in disarray amid the concerning form of Cuthbert and North - who suffered a first-half concussion after being kicked accidentally by Dave Attwood but failed to make impact upon returning.
It was hard to remember a Wales-England clash over the previous 125 editions of one of rugby's oldest rivalries that had been provided with more subtext and importance than the match which kicked-off the 2015 Six Nations.
Coming 232 days before the critical World Cup Pool A clash at Twickenham, England returned to Cardiff two years on from their championship and grand slam wreaking record defeat in Wales with Gatland plotting a similar fate.
While Wales were buzzing from just their second victory over major southern hemisphere opposition in 28 attempts last autumn, England arrived at the Millennium Stadium with a dozen first team players out injured and facing a wall of noise which had bewildered them 24 month previous.
To combat such vocal support England coach Stuart Lancaster had used giant speakers during training in an attempt to acclimatise to the cauldron-like atmosphere and ensure his side were not blown away again.
Early attempts to dilute the cacophony of noise from the Celtic crowd had proved successful as England opted to the Millennium Stadium roof to remain open on a brisk Welsh night but the scale of the task facing the visitors remained daunting with 290 caps given away to their hosts.
But within just 10 minutes, it was more than just experience that England conceded to Wales, and the Six Nations co-favourites powered into a commanding lead as after Leigh Halfpenny's penalty, Taulupe Faletau broke off the base of the scrum and fed Webb, who scampered over to score.
If England had appeared flustered in the early moments they displayed few nerves is storming their way back into the contest as Watson latched onto Mike Brown's grubber kick and claimed his maiden international score.
In stark contrast to their demoralising defeat in 2013, England were a firm presence in the contest but continual errors allowed Wales regularly encouragement, and Halfpenny punished the latest bout of ill-discipline after 25 minutes with a second penalty.
Ford reduced the arrears with his first Six Nations points but despite England presenting Wales with an opportunity to reestablish their eight-point lead, Halfpenny uncharacteristically missed a penalty from point-blank range.
However, in the final play of the first half the Welsh did add to their advantage as Biggar's drop goal ensured the home side had the last word of an absorbing first 40 minutes.
Yet it was a blow that would be wiped out within the opening minutes of the second period as a phase-laden attack from England ended as Joseph beautifully escaped George North and Webb to score under the posts.
The early try swung the momentum in England's favour and though James Haskell spurned the chance to claim a third try when he collided with the post, a yellow card for Cuthbert and Ford's subsequent penalty thrust them in front.
Victory appeared to have been secured when Dave Attwood went over but referee Jerome Garces chalked the score off due to an obstruction from replacement Nick Easter on Luke Charteris, much to Wales' relief.
However, it was a second life they were unable to grasp as England's defence held firm and their stubbornness was rewarded when Ford kicked his third penalty to confirm a famous win and shock Wales.
Wales: 15. Leigh Halfpenny, 14. Alex Cuthbert, 13. Jonathan Davies, 12. Jamie Roberts, 11. George North, 10. Dan Biggar, 9.Rhys Webb; 1. Gethin Jenkins, 2. Richard Hibbard, 3. Samson Lee, 4. Jake Ball, 5. Alun Wyn Jones, 6. Dan Lydiate, 7. Sam Warburton, 8. Taulupe Faletau.
Replacements: 16. Scott Baldwin, 17. Paul James, 18. Aaron Jarvis, 19. Luke Charteris, 20. Justin Tipuric, 21. Mike Phillips, 21. Rhys Priestland, 22. Liam Williams.
England: 15. Mike Brown, 14: Anthony Watson, 13. Jonathan Joseph, 12. Luther Burrell, 11. Jonny May, 10. George Ford, 9. Ben Youngs; 1. Joe Marler, 2. Dylan Hartley, 3. Dan Cole, 4. Dave Attwood, 5. George Kruis, 6. James Haskell, 7. Chris Robshaw, 8. Billy Vunipola.
Replacements: 16. Tom Youngs, 17. Mako Vunipola 18. Kieran Brookes, 19. Tom Croft, 20. Nick Easter, 21. Richard Wigglesworth, 22. Danny Cipriani, 23. Billy Twelvetrees.