David Moyes' side had lost only one in 20 league games heading into the clash and looked on course to keep their good start to the season on track as Steven Naismith gave them a half-time lead.
But despite dominating the first 45 minutes Everton could not clinch a second goal and a much-improved Reading made them pay as Le Fondre headed an equaliser before firing in a second from the penalty spot as the Royals picked up their maiden league victory in front of a record crowd at the Madejski Stadium.
Everton came close to opening the scoring inside two minutes as a Thomas Hitzlsperger corner was not dealt with and Phil Jagielka forced a smart reaction save from Adam Federici.
But the Toffees took the lead after 10 minutes after some woeful defending by Reading's back line. A hopeful ball out of defence was not dealt with by Reading on a number of occasions before Kaspars Gorkss' back-header fell straight to Nikica Jelavic. The Croatia forward looped a cross back into the box which was left by both Gorkss and Sean Morrison, with Naismith taking full advantage to slot the visitors in front.
Reading were almost level immediately as Tim Howard rushed out to clear a long ball but was beaten to it by Le Fondre, who could not keep his effort down as Howard scrambled back towards his goal.
As half-time approached Everton continued to be frustrated in their quest to find a killer second goal, as captain Jagielka saw his flicked header cleared off the line by Jay Tabb. Reading came out for the second half much more positively and forced two corners in the opening four minutes.
Le Fondre's equaliser came courtesy of a free-kick from Nicky Shorey after Hitzlsperger had caught Tabb on the left side of the Everton box and the former Rotherham striker was picked out superbly to head Reading level with 51 minutes on the clock.
Reading were awarded a penalty by Martin Atkinson as Seamus Coleman bundled into the back of Le Fondre, who brushed himself off to send Howard the wrong way and put the hosts ahead with a little over 10 minutes remaining.
Their lead was nearly wiped out instantly however as Marouane Fellaini headed Leighton Baines' corner against the post, with the loose ball falling straight to Federici. Reading then saw the game out in relative comfort to secure what could prove to be a vital three points.