The tournament's host nation must now beat Group A opponents Australia next Saturday to have a realistic chance of progressing to the quarter-finals.
Wales' triumph was hardly unprecedented, but World Cup context aside, there were a number of factors that made the result especially galling for England fans.
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1. Wales scored more points at Twickenham than ever before
Wales' 28 points was a new high score at Twickenham, reached in their 50th meeting with England at the stadium.
Only once before has a northern hemisphere side ever scored more at the home of English rugby - France scored 35 points in this year's final Six Nations game as England adopted a cavalier approach in a bid to score the points needed to win the championship.
2. It was the most points Wales have ever scored in a World Cup game (against a northern hemisphere side)
And only once before have the Welsh ever scored more against a Tier 1 side at rugby's showpiece tournament - notching 37 points in a loss to New Zealand in 2003.
3. Dan Biggar took the record for most points by a Wales player scored in a single World Cup match
No matter that Wales have played Namibia, Japan, Uruguay and Canada in Rugby World Cups - Biggar's 23 points (thanks to a 100 per cent success rate on seven penalties and one conversion) was a new record for a Wales player in a single match.
4. This was England's first loss to a northern hemisphere side in the World Cup group stage
Wales arrived at Twickenham depleted by injuries - and the casualty list only lengthened in the second half of the game - yet they still had enough strength to become the first northern hemisphere side to beat England in a World Cup group stage match and the first in the northern hemisphere tournament.
England have only lost to northern hemisphere teams twice before - on both occasions in New Zealand and in the quarter-finals at the 1987 World Cup to Wales, and the 2011 tournament to France.
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5. England have already conceded more points than they did in the group stage four years ago
England conceded 34 points in their 2011 group matches featuring Argentina, Scotland, Romania and Georgia. From half the number of games (against two tough opposition in Fiji and Australia) they've already conceded 39 points.
6. England threw away a seven point (or more) half-time lead for the first time in 27 games
England were 16-9 up at half-time. The last time they surrendered as big a half-time advantage was in February 2008 against Wales.