First-half goals from defender Reda Johnson and big striker Atdhe Nuhiu put Wednesday firmly in control and, after Leeds substitute Matt Smith had been sent off two minutes into the second period, Connor Wickham added a killer third.
Chris Maguire's deflected free-kick in the 67th minute and substitute Caolan Lavery's superb late double ensured Leeds slumped to their heaviest defeat of the season and, not since a 4-0 victory in October 1955, have Wednesday enjoyed such a comfortable win against their White Rose rivals.
Wednesday extended their unbeaten run to five matches and the manner of this latest success will surely convince chairman Milan Mandaric to make caretaker boss Stuart Gray the club's permanent manager.
On-loan Sunderland striker Wickham was one of three changes to
Wednesday's starting line-up, while Leeds' new signings Cameron Stewart and Jimmy Kebe both made largely ineffective debuts on the left and right wing respectively.
Wednesday were first to threaten, but winger Jacques Maghoma lost his balance when sent clear into the penalty area and Nuhiu headed Johnson's cross off target.
Defender Jason Pearce headed Leeds' first effort wide from Kebe's cross, while Wickham lashed a low angled shot inches wide at the other end after a swift Wednesday counter-attack.
The home side then took the lead. Wickham's free-kick was not properly cleared and midfielder Kieran Lee clipped a fine ball over the top to pick out Johnson in the penalty area and the unmarked defender had plenty of time to steer the ball home from six yards, off his shin, for his third goal of the season.
Wednesday were comfortably the more cohesive side and Maguire crashed in a low 25-yard shot that forced Leeds goalkeeper Paddy Kenny into a smart near post save.
Leeds began to find their range and enjoyed more possession, but Wednesday dealt the visitors a massive blow with a second goal just before half-time.
Wickham dispossessed Leeds skipper Rudy Austin and ran 30 yards before slipping the ball to Lee and he rolled the perfect pass across the six-yard box for Nuhiu to slide the ball home at the far post.
Wednesday could have been out of sight moments later when the impressive Lee set defender Liam Palmer free in the box, but he fired low into the side-netting.
Leeds were dealt another blow seconds after the restart when half-time substitute Smith was shown a straight red card by referee Lee Probert after colliding with Johnson.
Wednesday then struck their third, all but securing their fourth league win under Gray three minutes later.
Wickham's backheel spun kindly off Maghoma and the forward powered into the left edge of the area before drilling a low left-footed shot inside Kenny's near post.
Maguire's 25-yard free-kick after Austin's foul on Maghoma deflected off the Leeds skipper to wrong-foot Kenny and make it 4-0 in the 67th minute and Lavery, recalled from a loan spell at Plymouth this week, turned the visitors' defence inside out before netting in the 80th minute.
It could have been worse for Leeds, but Wednesday substitute Jermaine Johnson's stinging effort in the closing stages hit the post and Wickham's goal-bound shot was deflected over the crossbar by Leeds defender Pearce.
But still the fun for Wednesday was not over as Lavery turned on the edge of the area to curl home a fine sixth with virtually the last kick.