Winger Jimmy Kebe and striker Grzegorz Rasiak both scored twice and fellow forward Simon Church grabbed a spectacular goal as the resurgent Royals cruised to the three points.
Both sides kicked off hovering just above the relegation zone but Reading seemed to have turned the corner since Brian McDermott took charge and have gained confidence from their run to the FA Cup quarter-finals.
Owls boss Alan Irvine has work to do to prevent a drop into League One, however, after a wretched performance in which only goalkeeper Lee Grant impressed.
Wednesday were hit for six at the Madejski last season and will not relish a return to Berkshire in the near future.
Rasiak was making a rare start up front and came close to an opener inside two minutes but floated a header onto the roof of the net from Gylfi Sigurdsson's free-kick.
Wednesday midfielder Darren Potter then lashed in a drive from the edge of the area which was kept out by a strong wrist from Adam Federici before Rasiak went close again.
Sigurdsson was again involved on the left and after he retrieved a long ball from Kebe he found Rasiak in the area but the Poland international's header was tipped over by Grant.
Former England left-back Michael Gray then stung the palms of Federici after a swift counter-attack from Wednesday before the visitors' inability to deal with Rasiak almost cost them yet again.
Sigurdsson provided the delivery - this time from a corner - and Rasiak rose highest to thunder a header on goal but Grant made another fabulous stop.
The Royals were well on top and finally forged ahead in the 42nd minute.
Jay Tabb carried the ball forward down the right before squaring to Kebe 25 yards from goal. The winger unleashed a powerful shot which took a deflection off Richard Hinds to wrong foot the unfortunate Grant and find the back of the net.
And McDermott's side were quick to double their lead in first-half stoppage time after more good play from the excellent Sigurdsson.
The Icelander dribbled past two defenders inside the area before calmly picking out Church in space. Church's shot was well saved by Grant but only to the feet of Rasiak, who tapped into an open goal.
Irvine introduced Leon Clarke and Tommy Miller at the break but the home side took just seven minutes to increase their lead through Church's ninth of the season.
Rasiak flicked the ball on to his strike partner who looked to have been forced wide.
But the Wales striker cut in on his left foot and arrowed a stunning 20-yard strike across Grant and into the top corner via the upright.
Wednesday had all but given up and Rasiak made it four in the 65th minute. Kebe skipped down the right and played in a low cross to the near post where Rasiak slid in to hammer home.
And the in-form Kebe - who has often failed to deliver any final product for most of his Reading career - made it five goals in his last five games with the fifth in the 71st minute.
Centre-halves Hinds and Mark Beevers made a hash of clearing the ball and Kebe stole in to hammer an unstoppable shot into the roof of the net.