Yeovil again dictated proceedings at the start of the second half, with on-loan striker Andy Williams coming inches away from breaking the deadlock after hitting a curling effort narrowly wide.
However, Huish Park once again became the centre of controversy on 77 minutes after referee Trevor Kettle awarded the Royals a penalty after Luke Ayling was adjudged to have brought down Le Fondre.
The striker picked himself up and slammed past goalkeeper Wayne Hennessey to net his third league goal of the season and earn the visitors the valuable three points
In the first ever league meeting between the sides, Adam Le Fondre's penalty 13 minutes from time handed the Royals their first Sky Bet Championship win since the opening day - and condemned the Glovers to a fifth consecutive defeat in all competitions.
Reading manager Nigel Adkins made sweeping changes after the Royals' 6-0 humiliation at Peterborough United - with only Chris Gunter, Shaun Cummings and Le Fondre surviving the cull.
Adkins swapped Gareth McCleary for Danny Williams in a surprise first-half substitution and the newly-introduced midfielder came closest for the Royals before the break when he volleyed former Real Madrid and Everton winger Royston Drenthe's deep cross wide of the post.