Lacklustre Wednesday trailed 2-0 at half-time, with Reading deservedly ahead through goals from Pavel Pogrebnyak, a towering header, and Nathaniel Chalobah, a powerful half-volley.
Reading could have won by more but wasted a 63rd-minute penalty, when Hal Robson-Kanu’s poor spot-kick was easily saved by Keiren Westwood.
Wednesday went into the game in moderate form, with five wins in nine league matches but only one in their last four in all competitions.
Reading had been similarly inconsistent, with just one league victory in six games since Steve Clarke succeeded Nigel Adkins as manager.
However, Clarke did have two FA Cup successes under his belt, with Reading now due to travel to Derby for a fifth-round tie.
Wednesday began sloppily, with Garath McCleary crossing precisely from the right and Westwood having to palm it away to safety as Pogrebnyak rushed in.
Reading threatened again when Simon Cox burst clear on to a Robson-Kanu pass but Westwood did well to parry his shot.
Wednesday were showing little of substance going forward but did fashion a clear chance following a swift break.
Jacques Maghoma crossed low from the left-hand byline and Chris Maguire sent in a fierce drive that home keeper Adam Federici saved confidently.
It was a rare Wednesday visit into the home half and Reading were soon back in control, mostly through McCleary’s right-wing raids.
But his finishing was poor. He had a shot blocked after being released by Pogrebnyak and then blazed over from an incisive Chalobah pass.
However, Wednesday eventually paid for their lack of adventure, with Reading going ahead in the 29th minute.
Stephen Kelly sent in an excellent cross from the right and Pogrebnyak rose above everyone to firmly nod in his third goal of the season.
Five minutes before half-time, Reading stretched their lead. McCleary broke quickly from his own half and found Chabolah in space.
The recent loan signing from Chelsea took the ball first time on the half-volley to send a rasping effort past Westwood for his first Reading goal.
Federici saved superbly from a Lewis Baker piledriver but Reading swiftly reasserted their superiority after the interval.
McCleary thought that he had made it 3-0, when thundering in a shot after a lightning Reading break, but he had strayed offside.
Reading should have added a third in the 63rd minute, after Wednesday substitute Jeremy Helan brought down Pogrebnyak in the area.
But Robson-Kanu’s penalty was weak as well as poorly directed and Westwood made a comfortable save.
Wednesday did stage a late rally but Maghoma and substitute Claude Dielna wasted openings and Reading held on with ease.