The Lilywhites were decent in the first half and perhaps a touch unfortunate to be trailing at the interval.
However, the game got beyond them in the second half, a contentious penalty given against them the start of their downfall.
Domingos Quina gave the Hornets a ninth-minute lead, that after early chances for Sean Maguire and Brad Potts.
Watford went 2-0 in front eight minutes into the second half, Jordan Storey adjudged to have fouled Ismaila Sarr - replays showed no contact.
Troy Deeney hammered home the penalty but Tom Barkhuizen's deflected 25-yard strike brought PNE back into the game.
Nathaniel Chalobah volleyed the home side's third goal and the game became increasingly one-sided as they looked to turn the screw, creating a succession of chances.
That said, a strong penalty shout which Emil Riis had at 3-1 could have made things interesting, unfortunately it wasn't given.
Joao Pedro, on as a first-half substitute, completed the scoring with a close-range fourth goal.
That is seven goals conceded in two games for North End, this the first time they have conceded four in a match for 12 months.
There had been five changes to the PNE side from last Tuesday night's defeat to Blackburn, with Ben Davies, Ben Pearson, Storey, Brad Potts and Sean Maguire restored to the side.
As expected, Alex Neil went with a 3-5-2 formation to compensate for having no full-backs to choose from, Scott Sinclair and Barkhuizen playing as the wing-backs.
Although North End conceded early, they had twice gone close at the other end to opening the scoring inside the first seven minutes.
Maguire struck a rising shot from the edge of the 'D' which Ben Foster got fingertips to, turning it over the bar.
Barkhuizen then led an attack down the left, his pass slipping Maguire in behind the Watford defence down the channel.
Maguire held the ball up and then cut it back into the path of Potts who drove a first-time shot across goal and just wide of the far post.
So it was a blow when the home side went in front in the ninth minute.
Declan Rudd made a smart diving save to keep out Quina's shot and the ball fell out to the wing on Watford's right.
Jeremy Ngakia had too much time on the ball at that point to get it under control and lay it off to Ismaila Sarr behind him.
Sarr's cross was an excellent one, it staying quite low and dropping at the far post where Quina arrived to knock it past Rudd from inside the six-yard box.
A good save from Foster denied PNE an equaliser in the 24th minute.
When Potts was fouled by James Garner, Daniel Johnson lifted a free-kick into the box which Patrick Bauer initially won in the air.
It was cleared out of the box but Hornets striker Andre Gray inadvertently hooked it back into his own box.
Bauer was first to it to the left of goal but his shot was smothered by Foster who was alert to the danger.
Rudd made a big save right on the stroke of half-time, in fact the shot from Sarr was the last kick of the 45 minutes.
A cross from the left dropped across the box to the far post where Sarr met it on the volley, Rudd tipping it over the bar. Before the corner could be taken the whistle went for the interval.
There were three goals in a six-minute spell early in the second half as play swung one way and then the other.
A contentious penalty saw Watford double their advantage in the 53rd. Sarr went down in the box as he went past Storey, replays showing he had gone to ground before the PNE defender had made any sort of contact.
Referee Jarred Gillett pointed to the spot though, Deeney hammering the penalty down the middle into the roof of the net, Rudd getting a glove to it but power beat him.
A slice of luck came North End's way two minutes later to briefly bring them back into the contest.
Pearson's pass found Barkhuizen who brought the ball inside from the left before hitting a shot from 25 yards which struck Garner on the chest and flew into the net - wrong-footing Foster.
But before the hour mark had been hit, Watford had their two-goal lead back.
Chalobah played a pass to Deeeny on the edge of the box and continued his run to meet Deeney's flick and volley across Rudd into the far corner.
North End had a good shout for a penalty in the 61st minute, Riis bursting forward on to a long ball to hold off two defenders and get into the box.
Christian Kabasele appeared to clip him into the box and down the Danish striker went, but Mr Gillett waved play on.
Rudd made good saves in quick succession from Deeney and Sarr, the flow of the play very much with Watford at this stage who extended their lead with a fourth goal in the 74th minute.
It was a bit too easy, a corner from the right flicked on Craig Cathcart, leaving substitute Pedro with the simplest of finishes from three yards.
A chance of a consolation goal came North End's way in the 80th minute, Potts getting to the byline to the left of goal and crossing to find substitute Tom Bayliss - his header going straight at the keeper.
Watford: Foster, Ngakia, Kabasele, Cathcart (Sierralta 88), Femenia (Wilmot 70), Sarr, Chalobah, Garner (Phillips 88), Quina, Deeney (Perica 70), Gray (Pedro 31). Subs (not used): Troost-Ekong, Navarro, Crichlow, Bachmann.
PNE: Rudd, Storey, Bauer, Davies (Huntington 82), Sinclair, Pearson (Ledson 65), Johnson (Bayliss 79), Potts, Barkhuizen, Maguire, Riis (Stockley 79). Subs (not used): Holland-Wilkinson, Baxter, O'Reilly, Coulton, Ripley.
Referee: Jarred Gillett
Thanks for reading. If you value what we do and are able to support us, a digital subscription is just £1 per month for the first two months. Try us today by clicking here