It was a shocker of a start to the new season - the first game in front of fans at Deepdale for 17 months - there being few clues of the afternoon ahead for the Lilywhites when Emil Riis put them ahead in the eighth minute.
They lost Declan Rudd to a head injury early on, with his replacement Daniel Iversen beaten four times.
Hull got a grip on the game soon after falling behind and their 35th minute equaliser through the excellent Keane Lewis-Potter had been long coming.
Tom Barkhuizen saw two shots saved early in the second half before Hull went on to score three more.
Richie Smallwood's deflected shot went in off the post for the visitors' second goal, before two in the closing few minutes sealed PNE's fate.
Josh Magennis touched in Lewis-Potter's cross at the near post for the third goal in the 85th minute, substitute Andy Cannon's shot from a tight angle touching off a Preston leg to make it 4-1 in stoppage-time.
A change of formation at half-time couldn't get North End going, Frankie McAvoy switching from 3-4-1-2 to 4-4-2 in the second.
Riis started alongside Ched Evans up front, with Barkhuizen and Greg Cunningham operating at wing-backs.
Before kick-off, the PNE players formed a guard of honour to welcome Paul Gallagher on to the pitch, Gallagher having retired at the end of last season to join the coaching staff.
Inside the first couple of minutes, Rudd dashed to the edge of his box to challenge head first with Lewis-Potter who was chasing a through ball.
The Hull winger was offside but there was no flag at that point, Rudd having no choice but to clear with his head and collide with Lewis-Potter.
It was then that the flag went up for offside but Rudd was left down on the turf and needed treatment from the physio and club doctor before eventually getting back up to continue for the time being,
Play hadn't resumed for that long after the injury break when North End took the lead.
Alan Browne took possession in midfield and fed a pass out to Barkhuizen in acres of space down PNE's right channel.
Barkhuizen powered forward and sent a low cross into the middle which found Riis at the far post who slid the ball home.
Rudd's afternoon was to end after 13 minutes, the keeper clearly suffering the effects of the earlier collision.
He was replaced by Iversen, the change classed as a concussion substitution which have been introduced this season It allowed PNE to make three more subs, with Hull permitted to make four.
The Tigers bossed much of the first half play from then on, Lewis-Potter creating plenty of problems down the visitors' left side.
He had a penalty shout waved away after going to ground from Brown's challenge.
Hull equalised in the 35th minute, Smallwood sliding a pass behind the North End back line which Lewis-Potter reached on the left hand side of the box and finished with a low shot across Iversen on the angle.
On the stroke of half-time at the other end, Barkhuizen launched a long throw-in from the right into the box.
It came off a Hull head and fell to Riis who volleyed high over the bar.
North End made a double substitution at half-time, Sepp van den Berg and Brad Potts replacing Riis and Cunningham.
The system changed as well to a 4-4-2 diamond, Ben Whiteman sitting deep in front of the back four with Browne and Ryan Ledson on the sides and Potts at the point behind Evans and Barkhuizen.
Two chances fell the way of Barkhuizen early in the second half, the first in the 47th minute when his curling right-foot shot from the left corner of the box was tipped behind by City goalkeeper Matt Ingram.
Two minutes later the ball fell to him in the box after a misjudgement in the Hull defence, Barkhuizen's low shot on the stretch saved one-handed by Ingram diving low to his right.
Hull survived those two let-offs and went in front in the 63rd minute. The ball was worked to Smallwood on the edge of the 'D', his low shot clipping off Whiteman and wrong-footing Iversen before going in off the inside of the post.
North End rolled their last dice in terms of a substitution, Daniel Johnson coming off the bench to replace Whiteman - his deep role given to Ledson who had been quite fortunate to escape only with a yellow card for a forceful challenge on Malik Wilks.
Johnson added some craft in the engine room but precious in the way of chances followed, with Hull scoring their third goal five minutes from time.
It was a little too easy, Lewis-Potter having time on the left-wing to curl over a low cross right-footed to the near post area, Magennis nipping in behind a napping PNE defence to prod the ball past Iversen.
Hull weren't finished there, making it 4-1 in stoppage-time.
Substitute Tom Eaves chased the ball to the byline to the right of goal and back heeled it into the path of Cannon who fired home a low shot with the aid of s slight deflection from a narrow angle.
PNE: Rudd (Iversen 13), Storey, Lindsay, Hughes, Barkhuizem, Whiteman Johnson 69), Ledson, Browne, Cunningham (Cunningham 46), Riis (Potts 46), Evans. Subs (not used): Bauer, Rodwell-Grant, Thomas..
Hull: Ingram, Coyle, Jones, Smallwood, Emmanuel, Wilks (Smith 80), Docherty, Lewis-Potter (Scott 90) , Moncur, (Cannon 89) Greaves, Magennis (Eaves 89). Subs (not used): Fleming, Bernard, Baxter.
Referee: Gavin Ward (Surrey)