Reading went into the game on the back of Saturday's lacklustre display in a 2-0 defeat at Ipswich, but were in scintillating form against the Owls.
Kevin Doyle scored a hat-trick for the second successive home game while Andre Bikey celebrated his first start of the season with a goal and Noel Hunt marked his recall to the side with a brace.
Wednesday arrived brimming with confidence after beating Watford 2-0 at the weekend, but they never got going against the Royals.
Reading boss Steve Coppell said: "You don't know where a response like that comes from, you really don't.
"We prepare the same way for games and there's not much difference between the build-up to one match and another and yet some games it just sparks for whatever reason.
"It is really difficult for me to put my finger on it. It was chalk and cheese from the way we played on Saturday.
"We had a mentality to make amends and the start was important. I think it's important to get your noses in front in this league.
"The best teams can cope with going a goal down and still come back and I think we are still to prove to ourselves that we are capable of doing that away from home.
"On the evidence of the games we have had at home I think we could do it here (at the Madejski Stadium) but we still have something to prove to ourselves away from home."
Wednesday manager Brian Laws was equally baffled by his side's capitulation.
Although he lamented the fact their nightmare journey from Yorkshire to Berkshire did not help their cause.
"You couldn't recognise our team from Saturday. This was low in confidence and a yard or two off the pace, whereas on Saturday we were an organised team that defended tremendously well," said Laws.
"To give them two goals in the first 10 minutes was absolutely soul destroying because it knocked the stuffing out of us.
"The reaction that we got after that was panic and Reading smelled it and tore into us.
"The confidence we had after Saturday has been shattered after this. I can't put my finger on why we have performed like this."
Laws added: "The trip down here epitomised our day. We were stuck in traffic travelling down here.
"We left Sheffield at 8am and didn't get to Reading until 3pm, and that showed.
"We hit accidents on the M1 and the M40 and sitting it out on a coach for seven hours isn't great.
"I don't want to use too many excuses but that was a major factor.
"You prepare yourselves the best you can and try to get down here early, but when you have to stop at motorway services for the players to have food all your preparation goes out of the window."
PA Sport