Emphatic defeat for the Reds at Deepdale as the search for a first victory since the opening day of the season continues.
Despite levelling the game at 1-1 before the half time interval, Barnsley were well beaten in the second period at Preston.
Cameron McGeehan's first goal of the season had given the Reds hope of claiming something on their travels but it wasn't to be.
Head Coach, Daniel Stendel had made just the one change to his starting XI from the midweek draw against Derby, with McGeehan returning from injury to replace defender Mads Andersen; Toby Sibbick moving into defence in place of the Dane who dropped to the bench.
In what was a competitive start to the game with crunching challenges going in in midfield, the hosts began to carve out a few opportunities as the game settled down.
The very bright Daniel Johnson for the home side took aim from range on 11 minutes which forced Reds stopper Brad Collins into a parrying save with Sean Maguire then half-volleying the rebound weakly into Collins' hands.
Lively wide-man Maguire was in again for another chance on 18 minutes but Collins denied him brilliantly low down after Johnson had found the Irishman with a cut-back from the right-hand side of the box.
The visitors tried to gain some impetus as we entered the second quarter of the game, with Jacob Brown having the Reds' best effort. The Halifax-born winger fizzed a strike from the edge of the box wide after some exciting football in midfield had brokered the opening for him.
But the hosts were still looking the most likely to take the lead, and when Johnson capitalised on an Aapo Halme mistake, it took McGeehan to drag back the PNE man to thwart a clear breakaway. Cameron was booked for bailing out his teammate.
However, the opener did arrive and for the home side, on the half-hour mark.
After a Reds move broke down on halfway, PNE hit Barnsley on the counter and after Dave Nugent found his man just inside the box, a strong shot from Tom Barkhuizen was saved well by Collins but Johnson nipped in ahead of Toby Sibbick to head home the rebound from around five yards out, the ball looping up over the back-tracking Halme on the line.
Collins then had to be smart just minutes later to deny North End a second, a great stop with his feet to thwart Maguire again who'd been fed by the outstanding Johnson.
But the Reds did hit back before the break, against the run of play. Mike Bähre's corner kick towards the far post was stabbed goalwards by Conor Chaplin and after a block on the line, McGeehan slammed home the equaliser.
It was a clinical piece of football and the Reds headed into the changing room on level terms.
HALF TIME: PNE 1-1 Reds
Despite getting back to parity just before the break, that was soon undone with the second half proving disastrous for Barnsley as their hosts punished them four times for defensive errors.
On 50 minutes, Barkhuizen fired in having been played in by that man Johnson who had scampered away down the left after the Reds had passed up possession.
Just 10 minutes later Johnson stroked home the third and his second after North End had beaten the offside trap with a simple punt over the top.
Ex-Reds loanee Ben Pearson made it four for the hosts just five minutes later, tapping in on the goalline despite the best efforts of Collins and Ben Williams after Barkhuizen had burst clear of Halme down the Reds' right flank.
The victory was finished off by substitute Josh Harrop in the 79th minute as he lifted the ball over Collins after more questionable defending and the demoralised Reds fell to another defeat and now sit second bottom going into the international break.
FULL TIME: PNE 5-1 Reds
Collins, J.Williams (Green), Halme, Sibbick, B.Williams, Brown (Wilks), Mowatt, McGeehan, Bähre (Styles), Chaplin, Woodrow.
Unused: Walton, Andersen, Thomas, Pinillos.