Two late Leeds goals ensured a frantic finale but could not save Dennis Wise's side crashing to a third successive Coca-Cola Championship defeat in an extraordinary Yorkshire derby.
Marcus Tudgay's header gave Wednesday a seventh-minute lead and then two contenders for goal of the season from Chris Brunt and Jermaine Johnson put the visitors in control.
Not even the dismissal of Tudgay early in the second half could stop the rampant Owls sweeping into a 3-0 lead to leave Leeds rooted to the bottom of the table and staring at the abyss with only 10 games remaining.
Lee Bullen's late own goal was met with ironic cheers from Leeds fans, then Richard Cresswell clipped home a second a minute later, but it was too little too late.
After Tudgay's early opener Leeds had more than their fair share of chances to equalise and looked for long spells in the first half the more threatening side before Brunt's brilliant second.
The home side were then left crest-fallen after Johnson finished off a sweeping Wednesday move with a thumping drive just after Tudgay's early second-half dismissal.
New loan signing Radostin Kishishev made his debut for Leeds, but skipper Kevin Nicholls missed out due to a thigh injury.
Sheffield Wednesday were forced to make just one change with Richard Wood stepping in for Graham Coughlan, following the sudden death of his teenage brother.
Wednesday's travelling hordes, who had wasted no time in taunting their relegation-threatened Yorkshire rivals, were given more to cheer in the seventh minute when Tudgay opened the scoring.
Deon Burton had just hit the crossbar with a header from Brunt's corner and when the ball broke for Tommy Spurr on the left, the young left-back swung over a pin-point cross to where the unmarked Tudgay looped a fine header over Leeds goalkeeper Graham Stack.
Leeds almost equalised in the 15th minute when Wood's scuffed pass back fell to Cresswell 10 yards from goal, but visiting goalkeeper Iain Turner bolted off his line to smother the former Wednesday striker's shot.
David Healy squandered another gilt-edged chance to haul Leeds level in the 22nd minute when mis-kicking the impressive Kishishev's neat pass into the box.
Turner saved smartly with his feet to deny Healy again after the little striker had wriggled clear in the penalty area in the 30th minute.
Moore was thwarted by a last-ditch tackle and Rui Marques' volley from the subsequent corner was headed off the goalline by Frank Simek.
But just as Leeds looked likely to equalise Brunt delivered a cruel blow in exquisite fashion, robbing Frazer Richardson 35 yards from goal wide on the left and within the blink of an eye clipping the ball brilliantly home to give Wednesday a two-goal advantage.
Wednesday were down to 10 men four minutes after the restart when Tudgay was sent off for a second bookable offence.
The Wednesday goalscorer, shown a yellow card at the end of the first half for a foul on Moore, was given his marching orders for kicking the ball away.
But Leeds were three down soon after, cut to shreds by a picture-book effort worthy of goal of the season.
Brunt's arrowed pass down the line found Burton, he picked out Whelan and, having swept the full length of the field, the Republic of Ireland international fed Johnson, who smashed the ball home first time from 20 yards.
Cresswell clipped the crossbar with an overhead volley in the 71st minute, but for all their possession Leeds created few chances against Wednesday's 10 men, now content to sit on their lead and catch their rivals on the counter-attack.
Wednesday skipper Bullen put through his own goal in the 87th minute to ironic cheers from Leeds' fans and a minute later Cresswell clipped home a second following Robbie Blake's through ball to ensure a frantic finale.
But time ran out for the home side and the damage had already been done.
Teams
Leeds Stack, Richardson, Rui Marques, Heath, Lewis,Howson (Blake 46), Douglas, Kishishev (Carole 83), Moore,Healy, Cresswell.
Subs Not Used: Ankergren, Johnson, Foxe.
Booked: Healy.
Goals: Bullen 88 og, Cresswell 89.
Sheff Wed Turner, Simek, Bullen, Wood, Spurr,Johnson (Small 72), Watson, Whelan, Brunt, Burton (MacLean 84),Tudgay.
Subs Not Used: Adamson, Gilbert, Folly.
Sent Off: Tudgay (49).
Booked: Tudgay, Spurr, Burton.
Goals: Tudgay 7, Brunt 37, Johnson 54.
Att: 25,297
Ref: L Probert (Gloucestershire).