The Owls lost only their third game on their travels this season as first half goals from Pavel Pogrebnyak and Nathaniel Chabolah gave Reading a welcome win.
The visitors did launch a spirited comeback after the break after Keiren Westwood saved a Hal Robson-Kanu penalty but the damage was done and they made the long haul back to Sheffield with nothing to show for their efforts.
Stuart Gray shuffled his pack in Berkshire, going with a 4-3-3 formation and handing starts to Sam Hutchinson and Kieran Lee.
Manchester United loanee Will Keane led the line but the main talking points started at the other end, with Westwood central to the action.
First the in-form goalkeeper made a vital intervention to prevent a Garath McCleary cross falling at the feet of Pogrebnyak before Simon Cox was thwarted having burst in on goal.
In a lively start, Wednesday responded with Chris Maguire forcing Adam Federici into a diving save but the Royals promptly motored upfield and McCleary sliced wide after finding space in the penalty area.
And the hosts deserved the lead they fashioned on 29 minutes. Stephen Kelly delivered a teasing cross into the mix and Pogrebnyak was on hand to plant a firm header into the roof of the net.
There was more woe for the Owls five minutes later when Glenn Loovens picked up his tenth yellow card of the season, triggering a two-match suspension.
Then to compound matters, Wednesday went 2-0 down five minutes before the break.
A sweeping move ended with debutant Chalobah smashed home following good work down the right by McCleary.
Almost on the whistle, it could have been three but Loovens hooked off the line after Robson-Kanu showed enterprise to chip over Westwood.
And to sum up what had rapidly developed into a miserable first half, Federici denied Lewis Baker a maiden goal with a fine low save right at the last.
Wednesday made a double change for the second period, with Joe Mattock and Baker making way for Jeremy Helan and Atdhe Nuhiu.
And, forging a route back into the contest, the Owls were handed a huge boost 15 minutes in when Reading missed a golden chance to make the game safe.
Helan was adjudged to have tripped Pogrebnyak in the box and Robson-Kanu stepped up only to see Westwood dive to his right and smother the spot-kick.
That gave Wednesday the impetus to throw men forward and Jacques Maghoma went close on 75 minutes having taken a Nuhiu feed nicely into his path.
A goal then might have seen a different climax to an entertaining Championship clash but despite the Owls asking more of the questions with the clock counting down - Lee and Claude Dielna each went close - Reading held on to post their eighth home win of the term.
Reading: Federici, Kelly, Pearce, Pogrebnyak, Robson-Kanu (Mackie 77), Cox (Norwood 67), Obita, McCleary (Blackman 77), Chalobah, Hector, Williams
Owls: Westwood, Palmer, Lees, Loovens, Mattock (Helan 46), Maguire, Lee, Hutchinson (Dielna 67), Baker (Nuhiu 46), Maghoma, Keane