The hosts were well on top and took a first-half lead when the impressive Yohan Cabaye curled in a free-kick.
But after Pavel Pogrebnyak went close, Le Fondre scored with his first touch to turn in Jimmy Kebe's low cross.
And he earned Reading's first away win of the season when he gathered Kebe's nod down to steer past Tim Krul.
The comeback was reminiscent of Reading's incredible effort against West Brom last Saturday when they came from 2-0 down to win 3-2 with Le Fondre also playing a key part.
The result was the Royals' first ever victory away to the Magpies in eight attempts dating back to 1900
And the victory, which was their first away win at Newcastle, lifts Brian McDermott's side out of the Premier League bottom three and leaves the Magpies without a success in six games.
Just two points now separate the two teams and as much as the three points will encourage the Royals, it will also depress a Newcastle side who were on top for large parts of this match.
But more significantly it heaps pressure on boss Alan Pardew with Newcastle unthinkably in the relegation dogfight.
Owner Mike Ashley has stuck with Pardew since he arrived in October 2010 and atop six finish last season augured well for 2012/13. But it hasn't happened, and with last season's top scorer Demba ba sold to Chelsea, Newcastle look well short of the form of a year ago. True they have also suffered injuries to key players, but some how it looks more than that is the reason.
Today was pardew's 99th agme at the helm and his win ratio of 36% with Newcastle is reasonable enough. But the natives on Tyneside are getting restless and he can't have many more performaces like this left before Ashley takes action.
The fans are already vocalising their concerns as shown on The Newcastle United Blog website:
'Make no mistake about it – this was a shocking loss by Newcastle today after a first half in which Newcastle were much the better side and had 7 shots on target and Reading had none.
'But we have now lost 10 of our last 13 league games in the worst run in Newcastle’s Premier League history, and if something doesn’t happen soon to turn this shocker around – we are going to be relegated in May – we’re that bad – and we keep finding ways of losing games – that’s the biggest concern – we should have won this game today – but again we found a way to lose it.'
The result comes after a bad week for the club transfer wise with main target Loic Remy being hijacked last minute by QPR's Harry Redknapp. Mike Ashley was so concerned he is belived to have insisted he now gets involved in major deals to esnure they are delivered.