The Royals' No.9 came off the bench to secure a second consecutive comeback victory for Brian McDermott and heap more misery on the hapless Alan Pardew
The hosts took the lead on 36 minutes as Yohan Cabaye curled a perfect free kick past Adam Federici, but substitute Le Fondre struck twice in six minutes to secure the Royals' second consecutive comeback victory.
Shola Ameobi returned from suspension to replace Gabriel Obertan on the right wing, while Yohan Cabaye made his full comeback to first-team action in midfield after a two-month absence due to a groin injury, in the hosts' only two alterations from last week's 0-0 draw at Norwich.
Brian McDermott made three changes from the side that started Reading's miraculous comeback victory over West Brom last week, with Stephen Kelly handed a debut at right-back.
The game was slow to get goping but the Royals had a great chance to score in the 12th minute as Jimmy Kebe raced onto a long ball down the right flank, but could only cut into Mike Williamson as he reached the box.
The hosts responded brilliantly and after Yohan Cabaye had a near-post effort saved by Federici, he clipped a lovely ball into Papiss Cisse in the box, but the onrushing Australian tipped Papiss Cisse's header behind.
Cisse was denied by a superb Alex Pearce block from opening the scoring on 26 minutes, but Garath McCleary stormed down the left immediately, cutting the ball to Pavel Pogrebnyak who could only turn the ball wide on the slide from 12 yards.
The Magpies' No.9 could only fire straight at Federici after fine work from Anita and the Royals keeper denied the Toon No.9 from point-blank ranged after Mathieu Debuchy burst down the right and found Cisse with a superb cross.
The Magpies finally made the breakthrough after the half-hour. After Sylvain Marveaux was felled making his way towards the area, Cabaye stepped up and curled a perfect free kick into the top corner from 20 yards.
The Royals had the better of things after the break, but had little to show for their dominance. Harte curled a free kick that was almost deflected in by a Newcastle leg, before Pogrebnyak rasped an effort well over the bar from 20 yards out.
Reading did get itself level on 71 minutes as Jimmy Kebe was afforded too much space on the right and he whipped a dangerous ball across goal that substitute Le Fondre bundled home with his first touch.
Pardew responded by replacing the superb Cabaye with Gael Bigirmana to the home fans' fury and they were apoplectic soon after as Le Fondre pounced on Hope Akpan's scuffed shot to bury his second and complete the Royals' comeback.
The hosts had a great chance to level scores late in the game, but Cisse could only shank his effort over as the ball landed at his feet eight yards out.