Ten men beaten
Sheffield Wed 2 (Maguire 10 pen, Afobe 57)
The Royals recent home record was turned upside down after a ninth minute red card and subsequent penalty handed in-form Sheffield Wednesday an early advantage that they never relinquished.
Chris Kirkland had denied both Pavel Pogrebnyak and Adam Le Fondre in an opening five minutes that suggested Reading could win again in front of their home support.
But Alex Pearce was sent off for bringing Benik Afobe to ground inside the box and Chris Maguire sent McCarthy the wrong way with his spotkick.
Nigel Adkins' men pressed for a way back into it and at times looked capable of overcoming their numerical disadvantage, but Afobe pounced on a spilled McCarthy save to add a second and make the mountain too much to climb.
Att: 19,772 (1,794 away)
Alfie scampered onto a good ball over the top of the Owls defence first, Chris Kirkland doing well to deny the Royals striker in a one on one situation.
The game was turned on its head in the 9th minute, when Alex Pearce was adjudged to have floored Afobe inside the Royals box. Referee Keith Hill pointed to the spot and issued a straight red card to the Reading centre back, before Chris Maguire slotted home from the spot.
Garath McCleary reverted to right-back and Chris Gunter slotted into the middle, but it was Reading who almost carved open the Wednesday defence soon after the sending off, Akpan somehow dinking a cross over Kirkland from the byline but no-one there to nod it home.
Naturally, with the numerical advantage, Wednesday were finding space in the final third and Gunter did brilliantly to come across and block a strike from Maguire that was destined to trouble Alex McCarthy. Maghoma was proving the root of most of our problems.
Reading were impressing with ten men and came within a whisker of equalising through their captain. A deep cross from Alfie on the right was nodded back into the box by Pogrebnyak and it was only cleared as far as McAnuff on the edge of the area, who volleyed inches wide with a thunderous effort.
Pogrebnyak ran towards the edge of the box but with five men around him had no option but to shoot from distance, fizzing a left-footed effort wide of the top left corner, ten minutes before the break.
But before half-time, former Royals loanee Benik Afobe almost doubled the visitors' lead, scurrying into the area and smashing it past McCarthy and against the top of the crossbar. And McCarthy did well to save a Maguire shot after the winger had dispossessed Obita and cut in from the right to drive a low effort on target.
Ex-Royal Michail Antonio was introduced by Stuart Gray at the break, replacing McCabe in midfield and in the opening minute of the second half he almost got on the scoresheet. Maghoma escaped down the left and slid a ball into the unmarked Antonio, whose sidefooted striker was brilliantly saved by the sprawling body of McCarthy.
Maguire then skied an effort high over the bar from the resulting corner, as Wednesday looked to put the game to bed. But a marauding McCleary run early in the second half ended with a nice pass into the feet of Pogrebnyak, who couldn't get it under control on the edge of the area to get a shot away.
Before the hour though, the Owls did get the second goal that it looked like they might need. Alex McCarthy could only half gather a bobbling shot driven at his goal, and Afobe was there to pounce on the loose ball and turn it home six yards out.
Jeremy Helan then struck the left post with a powerful effort that had beaten McCarthy as Wednesday pressed home their advantage, then just after the hour Maguire almost toed it round McCarthy for a third - but the Royals stopper expertly smothered the ball at the midfielder's feet.
A dangerous McCleary cross caused some panic in the Owls box and Guthrie recycled it, dinking the ball delightfully into Le Fondre, but the striker was flagged offside as he looked to pull the trigger.
Substitute Nuhiu sprung the offside trap to race into space and into the box with ten minutes left, but he dragged his shot harmlessly wide of the target.
Guthrie's cross into the box resulted in a proper goalmouth scramble, Kirkland trying to cling onto the loose ball with his legs as three Reading players and a number of Owls defenders all tried to stab it either towards goal or away from danger, but in the midst of a storm the Wednesday keeper finally gathered it into his body.
The Royals refused to give up, but McCarthy had to deny Nuhiu in injury time and, having played so long with only ten men, the home side began to tire and in swirling winds and relentless rain Wednesday saw the game out with relative ease.