Dan Biggar landed a late penalty as Wales defied a host of second-half injuries to edge England 28-25 in a compelling World Cup showdown at Twickenham.
A furious clash was tied 25-25 with eight minutes to go after scrum-half Gareth Davies touched down under the posts, setting up a heart-stopping climax that ended when Biggar hit the mark from 50 metres.
In the closing moments, England decided to kick for touch and launch an attacking line-out instead of taking shot at goal, but the gamble failed a Wales held firm.
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The hosts led 16-9 at half-time with Jonny May crossing, but they should have been in a more comfortable position given their ascendency founded on a strong set-piece that had seen the flaws witnessed in recent weeks ironed out.
Owen Farrell's kicking kept them in the driving seat - the Saracens fly-half finished with 20 points - but Wales grew in stature as the match neared its conclusion, drawing on all the experience of their big game players to see them home in a famous victory.
Stuart Lancaster conceded the visit of Wales and Australia to Twickenham over successive weekend would define his reign as head coach and he must now hope his players perform a rescue act against Australia next Saturday.
It is a match the World Cup hosts can not lose if they are to progress to the quarter-finals and the Wallabies will be scenting blood.
Lancaster made the biggest selection call of his three-and-a-half-year reign by starting Farrell in place of George Ford and picking Sam Burgess at inside centre and his return was a fine performance by Farrell and a mixed evening from Burgess.
The star of the evening, however, was unflappable man of the match Biggar who finished with a 23-point haul comprising of seven penalties and a conversion.
Wales saw Scott Williams and Liam Williams driven off on the medical cart in the second half and also lost Hallam Amos to injury, depleting the squad's resources ahead of Thursday's showdown with Fiji.
Conceding two penalties inside the opening 90 seconds was not the start England were aiming for and Biggar drew first blood by sending the second between the uprights.
Wales were suffering at the scrum and when a second was driven backwards Farrell was able to land a long-range penalty, the kick offering respite amid a breathless start to the 127th meeting between the rivals.
Biggar failed with an ill-advised drop-goal but made amends with three points from the tee before Ben Youngs almost slipped through a gap that appeared temporarily in the wall of red shirts.
A drop-goal from Farrell was not a thing of beauty but it found the mark to level the score at 6-6 heading into the second quarter and soon after Mike Brown and Sam Warburton squared off as tempers frayed over a tackle by Dan Lydiate on Tom Wood.
For the third time Wales' scrum was demolished and while Farrell obliged with the three points, better was to come from England when they ran in the first try in the 27th minute.
Line-out ball was worked to Anthony Watson who was tackled without a moment to lose but the hosts persisted, creating space down the blindside that Ben Youngs exploited clinically by sending May over.
A critical moment had arrived for Wales as they struggled to make an impression on the gainline and continued to suffer at the set piece, but they responded by finishing the half with a flourish when Scott Williams took advantage of Burgess drifting out of position to race through the midfield..
The outside centre was unable to produce the final pass, but the run led to a penalty from Biggar that was cancelled out early in the second half when Farrell replied in kind.
An unbearably tense third quarter continued with the fly-halves exchanging kicks and while England remained in control, Wales were still a threat and underlined the point when George North charged out of his 22.
The Welsh trailed 22-18 heading into the last 20 minutes courtesy of Biggar's laser-guided boot, but their cause was dealt a blow when Scott Williams was carried off on the medical cart.
Play swung frantically from end to end, Twickenham rising to its feet when Richard Wigglesworth and May combined down the left before wing Hallam Amos came to Wales' rescue.
A nerve-shredding finale was assured when substitute Lloyd Williams chipped ahead after a break down the left wing and Gareth Davies was the first to arrive, gathering and falling over the line with Biggar converting.
Biggar saved his best to last by landing the match-winning penalty from inside his own half to end England's seven-match winning run at Twickenham.
There was still time for England to have one last chance, winning a penalty with two minutes left, but the call to play on and not take a shot at goal ended in them coughing up possession from the line-out.