The 2-1 victory was the start of an 11-game unbeaten run for PNE while it also spelt the end for Peter Shreeves who resigned as Owls boss the following morning.
David Moyes’ men had trailed at the interval to a goal from Gerald Sibon.
But within 38 seconds of the re-start, Mark Rankine scrambled an equaliser.
Then 10 minutes from time, Jon Macken lifted a shot into the net for the winner.
To rub the salt into the wounds of the hosts, it was former Wednesday striker Richard Cresswell who got the crucial touch to play in Macken – Cresswell had come on moments earlier as a sub.
It was not North End’s most polished performance of the season, Moyes admitting that it had been a case of getting the job done. In their previous game, they had played some good football only to get beaten by a last-gasp goal at Crewe.
So for this Tuesday night visit to South Yorkshire, Moyes focused on finding a way to win. And North End started well, Sean Gregan going close after spotting that keeper Kevin Pressman had strayed off his line.
The skipper’s shot was on target but Pressman got back and chose to head clear even though he was in the box.
Wednesday took the lead in the 27th minute, North End left-back Rob Edwards judged to have fouled Sibon out by the touchline. The award of a free-kick brought protests from Moyes and No.2 Kelham O’Hanlon but to no avail.
Their mood did not get any better when Alan Quinn’s free-kick was headed home by Sibon.
At the interval, Moyes made a substitution with Paul McKenna replacing winger Iain Anderson. McKenna had not even had a touch of the ball when PNE pulled level.
They won a corner on the right, Graham Alexander’s flag-kick met by Gregan at the near post, who flicked it on into the middle.
Michael Jackson pushed the ball goalwards with his knee and Rankine forced it over the line from close range.
It was Rankine’s second goal in four days after he had been on target at Crewe.
Having gained confidence from the equaliser, North End pushed on in the search for a second goal. David Healy saw a shot blocked by Carlton Palmer and McKenna tried his luck with a shot from 25 yards which Pressman saved.
Rankine had another sight of goal, only from further out this time, his effort going straight at Pressman. Moyes went for a change up front as the clock ticked by, choosing to take Healy off and put Cresswell on.
The Preston boss revealed afterwards that it had been a toss-up between Healy and Macken as to who would come off. Thankfully, as it turned out, he left Macken on the pitch and the striker supplied the winner.
Cresswell came on as PNE prepared to take a free-kick.
Jackson delivered it into the box, Cresswell got above Danny Maddix to head the ball into the path of Macken, who darted ahead of Palmer to shoot over Pressman into the roof of the net.
PNE saw out the game and went on to win four matches in a row. Their next win came when Macken scored from 45 yards to help them beat Manchester City 2-1 at Deepdale.