PNE took the lead through Tom Barkhuizen in the first half before an error from Billy Bodin allowed Stefan Payne to round Conor Ripley and tap into an empty net.
Alex Neil started the game with the same side that finished the win over Salford City on Saturday and North End had the opening chance less than a minute into the game, Paul Gallagher playing a ball in behind for Barkhuizen who broke the offside trap, he squared it back to Brad Potts who directed his side footed effort past the far post.
Josh Harrop released Jayden Stockley in behind from the edge of the area, the target man looking for the far corner on his left foot but overcompensating.
Otis Khan ended the near 20 minute wait for another shot on target, cutting inside from the left to try to wrap his foot around the ball, his strike straight into Matt Hudson.
Just before the half hour mark, Potts delivered a cross to the far post, Harrop kept it alive and it fell to Gallagher on the volley who connected well with the ball but sent it over the bar.
North End went extremely close through Stockley who was just inches from opening the scoring. Rafferty's deflected cross was nodded on by the no.20 but as it looked destined to find its place inside the post, Joe Murphy reached to keep it out.
PNE would break the deadlock just minutes later, in the 33rd minute, Brad Potts played a ball for Barkhuizen to attack down the right side of the area and the winger placed it under the Rovers 'keeper, deflecting off the stopper and high into the net.
Just two minutes before half time Corey Blackett-Taylor stole possession on the edge of the PNE box before bending his shot high and wide past the far post.
The first chance of the second half came five minutes into it, a sweeping move forward from the visitors with Stockley pulling the ball back to Potts who struck first time, only into the arms of Murphy.
Another break from North End right on the hour mark gave the starting XI their last chance of doubling the lead. Barkhuizen getting in behind onto a deflected clearance, laying the ball into Potts' path who found Harrop six yards out be sliding in he could not direct it goalwards.
Preston then changed their entire XI, their team for the final 30 minutes being: Ripley, Browne, Bauer, Storey, Hughes, Ledson, Bayliss, Bodin, Johnson, Sinclair, Maguire.
It would take 12 minutes for the next chance in the game. Ryan Ledson's cross from midfield met by Sean Maguire who nodded the ball on, but it was easy for the home 'keeper.
10 minutes from time PNE would have another chance, nice work from left to right in the area left Alan Browne with the chance to poke the ball at goal, though the Irishman couldn't find the target from around 12 yards out.
More neat work down the right side of the area between Maguire, Andrew Hughes and Scott Sinclair presented the former with a chance after turning his man, but the striker's effort in the end was tame.
The home side were presented with a golden opportunity to level things up with less than five minutes remaining, Hughes trying to turn when facing his own goal and giving the ball to Stefan Payne who had time one on one with Ripley. The North End 'keeper stood up to the task and saved well with his legs.
Payne would have his goal two minutes from time, Bodin's back pass from the half line falling way short of Ripley who rushed out and was beaten to it by the Tranmere striker, who casually ran the ball towards an empty net before scoring.
With little time to find an equaliser, a well struck effort from Ledson was turned behind before an acrobatic volley from Hughes from the resulting corner, but it wasn't enough for the visitors.
PNE Starting XI: Hudson, Rafferty, Huntington, Davies, Earl, Pearson, Gallagher, Barkhuizen, Potts, Harrop, Stockley.
PNE Subs: Ripley, Bauer, Storey, Hughes, Browne, Ledson, Johnson, Bayliss, Baxter, O'Reilly, Bodin, Sinclair, Walker, Maguire.
Tranmere Rovers XI: Murphy, Macdonald, Clarke, Monthe, O'Connor, Morris, Banks, Spearing, Blackett-Taylor, Khan, Vaughan.
Tranmere Rovers Subs: Jones, Ellis, Nelson, Ray, Payne, Ridehalgh, Walker-Rice, Lewis.