Reading's Republic of Ireland international striker Kevin Doyle has now scored more league goals this season than the entire Crystal Palace team.
Neil Warnock's side scored twice, the first goals they have scored in the league, but Reading won the points thanks to a second-half hat-trick from Doyle.
Reading manager Steve Coppell gave league debuts to defender Alex Pearce and midfielder Jem Karacan. Both are products of the Reading academy system and won their places after fine displays against Luton in the midweek Carling Cup tie.
But it was old hand James Harper who shot Reading in front after Julian Speroni could only parry Stephen Hunt's shot.
Reading looked well on top but then Harper handled a Nick Carle shot and the Aussie took the penalty himself to level the scores.
Ten minutes into the second half Palace stunned Reading by taking the lead as Tom Soares outjumped Harper before bringing the ball under control and scoring from close range.
Then Doyle, the subject of much transfer talk as the deadline approaches, took over. First he tucked in Hunt's corner and then scored from Karacan's cross.
He laid claim to the match ball with a close-range header after being set up by Pearce.
When these two sides last met at the Madejski Stadium in 2005, Reading won 3-2 and fans later voted it their favourite match of Reading's Championship-winning season.
There's no love lost between Warnock and Reading supporters, so this is another win they will savour.