Goals from Brad Potts and Andrew Hughes completed a second-half turnaround to earn all three points against Stoke City.
PNE fell behind inside the opening minute of the second half following a superb strike from 30 yards by Stoke defender Ben Wilmot, but Potts drew his side level with a remarkable goal of his own, sending a scissor kick beyond the goalkeeper.
Hughes then rose highest on 81 minutes to head home a Ben Whiteman corner to seal the victory on the road.
Ryan Lowe made two changes from his first game in charge against Barnsley last month, bringing in Potts at right wing back in place of Ali McCann, while Ched Evans came in up top to replace Sean Maguire.
North End had the first effort on target in the 11th minute with an attack – started by skipper Alan Browne – ending in Ben Whiteman’s long-range strike being collected by goalkeeper Adam Davies at the second attempt.
PNE came forward again a few moments later, this time through Daniel Johnson, who slotted the ball across goal for Evans, but defender Danny Batth blocked his effort from six yards.
The side in green felt hard done by after 20 minutes after Browne appeared to be clipped from behind inside the area, but referee Jeremy Simpson saw nothing wrong.
At the other end, Stoke City almost opened the scoring, with Batth rising highest on the end of a corner, and Hughes’ block fell kindly to Steven Fletcher, but he couldn’t adjust to find the target from close range.
The rest of the first half didn’t see any chances created for either side, however straight after the break the hosts put themselves in front with an unstoppable shot from the right foot of defender Wilmot from all of 30 yards.
Ryan Lowe’s side weren’t behind for long, though, as Johnson sent a good ball towards the back stick where Potts was waiting to volley home with a superb scissor kick, before racing up to the delirium in the away end.
That gave PNE all the momentum from that point as they pushed forward for a quickfire second, but it was Daniel Iversen that was the next goalkeeper called into action, as he was forced to save low to his left on 78 minutes to deny Alfie Doughty.
A few minutes later North End took the lead with Hughes rising highest and sending a fantastic header past Davies in goal from Whiteman's corner to win his side all three points on the road.
Stoke City line-up: Davies; Wilmot, Batth, Chester, Fox; Clucas, Allen, Vrancic (Brown, 75); Campbell (Doughty, 69), Fletcher (Surridge, 52), Ince. Subs not used: Bonham, Smith, Brown, Oakley-Boothe, Wright-Phillips.
PNE line-up: Iversen; van den Berg, Bauer, Hughes; Potts, Browne, Whiteman, Johnson (Ledson, 88), Earl; Riis (Sinclair, 80), Evans (Maguire, 89). Subs not used: Ripley, Lindsay, McCann, Rafferty.
Attendance: 20,002 (1,603 PNE fans)
Referee: Mr J Simpson