Tom Barkhuizen, Brad Potts (2) and Josh Murphy (2) found the net in a dominant first 45 minutes at Euxton.
The took their foot off the pedal in the second half but still struck the woodwork twice and Scott Sinclair saw a penalty saved.
For Barkhuizen, it was his first slice of action since the opening game of the season, Covid having laid him low.
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He got through the full 90 minutes, that valuable mileage in the tank after the long lay-off
Carlisle had the first sight of goal, Taylor Charters' pass playing Zack Clough through in the box but he pulled his shot across goal and wide of the post.
North End took a seventh minute lead, Barkhuizen charging down a clearance from goalkeeper Adam Smith before rolling a shot into the empty net.
The second goal came six minutes later with Barkhuizen turning creator. He got room down the right-wing and sent over a cross which Potts met on the volley at the far post from six yards.
At the other end, Clough's shot from 20 yards was finger-tipped over the bar by Declan Rudd.
A couple more chances fell PNE's way. Jamie Thomas saw a shot blocked, then from Thomas' corner, Liam Lindsay's header was pushed out by the keeper.
Three goals in nine minutes in the run-up to half-time left the destiny of the contest in no doubt.
In the 34th minute, Adam O'Reilly throw in fed Potts down the right hand side of the box. Potts drove a low ball across the face of the six-yard box which Murphy finished at the far post.
Three minutes before the interval, left-back Joe Rafferty crossed low for Potts to side-foot in.
North End's fifth goal came in the 45th minute, a long ball from the back skimming off the head of Carlisle defender Max Kilsby and leaving Murphy with a free run on goal,.
Murphy moved into the box and slipped a low shot past the keeper.
PNE started the second half well, Joe Rodwell-Grant meeting a cross from Lindsay - who had stayed forward after a corner - and looping a header over the bar.
Smith tipped a shot from Barkhuizen on to the top of the bar, before the keeper denied Murphy a hat-trick just past the hour.
Barkhuizen's pass played in Sinclair behind the Carlisle defence on the right. Sinclair lhung a cross up to the far post which Murphy headed goalwards, Smith diving to push it away.
North End were awarded a penalty in the 68th minute, Rodwell-Grant brought down by the keeper as he tried to take the ball round him.
Murphy wanted to take it but Sinclair pulled rank to step up, Smith parrying his effort and also keeping out Rodwell-Grant's follow-up.
Both sides hit the woodwork in quick succession. Thomas, impressive throughout in a central midfield role, pulled the trigger from 30 yards and saw his shot striker the bar and go over.
Carlisle's Manasse Mampala's low shot from an angle on the left hand side of the box, hit the outside of the near post.
PNE: Rudd, O'Reilly, Huntington, Lindsay, Rafferty, Sinclair, Thomas, Potts, Murphy, Barkhuizen, Rodwell-Grant (O'Neill 76). Subs (not used): Baxter, Nevin, Leigh, Hudson.
Carlisle: Smith, Barnett (Fishburn 46), Devine, Ellis (Watt 67), Leslie, Mampala, Kilsby, Charters, Bell, Clough (Carr 60), Abrahams (Garvey 78)...
Referee: Jacob Graham