Goals from Shane Long, a terrific free-kick from Ian Harte and Noel Hunt gave Reading the points at Portman Road.
Long was the stand-out player in the game and had already threatened before being left alone to head in Brian Howard's corner on 18 minutes.
Grant Leadbitter went close with a free-kick and Andy Drury sent a shot straight at Alex McCarthy before the Royals added a second five minutes from time with a left foot free-kick from Harte.
Two minutes later Reading made it three when Noel Hunt galloped clear and rounded Marton Fulop to score with ease before Connor Wickham fired in a volley as a consolation for Blues in added on time.
Town made two changes to the side that won at Cardiff at the weekend, Drury and Darren O'Dea coming in for the injured Jimmy Bullard and Mark Kennedy. Reading started the brighter but it was Town who had the first effort at goal, Jason Scotland spinning away from his marker and firing low at Alex McCarthy.
The Royals lost skipper Matt Mills before the quarter hour, Ivar Ingimarsson his replacement but on 18 minutes the visitors were in front, Long left alone to head in from Brian Howard's corner. Hunt was booked for kicking the ball out of the ground in celebration.
Long, a constant threat throughout the first-half with his movement, fired over before Town had another scare just past the half hour, Damien Delaney hacking the ball off the line after Hunt had made contact from Howard's free-kick.
Paul Jewell's side enjoyed their best moments of the first-half in the closing 10 minutes, Leadbitter sending one of his trademark free-kicks - a flick up and volley - just wide.
Drury tested McCarthy with a powerful strike after Scotland had set him up, Leadbitter then shooting over after good work by Carlos Edwards.
It took a smart save from Fulop to keep Blues in the game just before the break though, again Long the threat but the Town 'keeper did enough to keep out his goalbound effort.
McCarthy held firm from Leadbitter's shot inside the first minute of the second-half , Drury then sending the ball over the bar from close range following Scotland's cross with Lee Martin ready to pounce.
Reading went close to extending the lead on 55 minutes, Fulop beating out Long's right foot effort and Howard sliding the ball past the post seconds later.
Town made a first change on the hour, Tamas Priskin on for Scotland to freshen up the attack, the Hungary international immediately sending a header at McCarthy from Martin's cross.
Long sent a diving header wide at the nearpost as he continued to carry the main threat to the Blues' goal while at the other end Gareth McAuley and Martin were both denied following Drury's free-kick.
Luciano Civelli replaced Drury for the last 20 minutes, Fulop cutting out the danger from Howard's cross as Long and Hunt looked to convert.
Brynjar Gunnarsson cleared the danger after good work by O'Dea down the left, Hal Robson-Kanu picking up a booking for the visitors after delaying a Town free-kick.
It was a free-kick that settled the game five minutes from time, Martin penalised for a foul and Harte sent a superb left foot effort into the corner.
Hunt extended the Royals' advantage a minute later with a cool finish before Wickham scored a consolation for Blues with virtually the last kick of the game.
Town's disappointment was enhanced with a yellow card to David Norris, meaning the skipper now faces a two match suspension.
Town: Fulop, Edwards, McAuley, Delaney, O'Dea, Martin, Drury (Civelli 71), Leadbitter, Norris, Wickham, Scotland (Priskin 62). Subs not used: Lee-Barrett, Peters, O'Connor, Hyam, Smith. Booked: Norris.
Reading: McCarthy, Gunnarsson, Mills (Ingimarsson 15), Khizanishvili, Harte, Howard, Leigertwood, Karacan, Robson-Kanu, Long (Church 90), Hunt. Subs not used: Andersen, Antonio, Taylor, Morrison, Manset. Booked: Hunt, Robson-Kanu.
Att: 17, 308