Reading centre back Alex Pearce was sent off in only the ninth minute after conceding a penalty.
Chris Maguire slotted home the spot-kick and, despite depleted Reading's valiant efforts, Wednesday comfortably built on their lead and cruised to victory, with Benik Afobe added a second goal from close range in the second half.
Both sides went into the game in rude health. Reading had won four of their previous five matches, scoring 16 goals in the process - 12 of them in their past two home games against Bolton and Blackpool.
Wednesday were unbeaten in 10 in all competitions and had lost only twice in 14 outings since Stuart Gray stepped in to replace Dave Jones in December.
Reading were unchanged for the sixth successive match and could have gone ahead in only the third minute through Adam Le Fondre, who scored hat-tricks in the wins over Bolton and Blackpool and was named Sky Bet Championship player of the month for January.
Le Fondre strode through the defensive cover alone but Wednesday goalkeeper and captain Chris Kirkland dived at the striker's feet, as he tried to go around him, and managed to retrieve the ball.
Pavel Pogrebnyak might also have given Reading the lead soon after. He flicked the ball past Kirkwood but, as it trickled towards goal, central defender Miguel Llera got back to clear it off the line.
Reading soon paid for their misses. Pearce had already been troubled by the pace of Afobe and, after Afobe had burst past him yet again, the Reading centre-back clumsily bundled over the striker.
Referee Keith Hill ruled a penalty and straight red card for Pearce. Maguire kept his nerve and drilled the spot-kick past Alex McCarthy.
Wednesday - also through to the FA Cup fifth round, in which they play Charlton at home - could have extended their advantage as the game degenerated into a tetchy affair. Keiran Lee had a shot well blocked by Chris Gunter.
Reading created efforts for Jobi McAnuff and Pogrebnyak, both blazed wide, and Wednesday went close near half-time, with an angled Afobe drive clipping the top of the crossbar and McCarthy saving well from Maguire.
Wednesday maintained their dominance after the interval, with Michail Antonio, a half-time substitute, forcing a good stop from McCarthy. It was only a temporary reprieve, though.
In the 58th minute, McCarthy made a bad error when fumbling Maguire's tame shot and Afobe followed up to tuck home. It could have been 3-0 soon after but McCarthy tipped a Jeremy Helan shot on to his near post and away to safety.
However, it was of little consequence, with Wednesday eventually strolling to the three points.