Two headers from Australia international Jackson Irvine sandwiched a fine finish from Alan Browne and saw the three points disappear off to Humberside.
North End's best spell in the game came early in the second half, Browne's 25-yard equaliser followed by a handful of decent chances.
They had been flat in the first 45 minutes, falling behind to Irvine's 28th minute goal.
Browne levelled two minutes after half-time and for a time it looked like Alex Neil's men could push for a winner.
But Hull had never looked out of the contest, looking dangerous on the counter-aattack.
Their winner came 10 minutes from time, Irvine nodding home his second goal of the game after a Kamil Grosicki corner had caused havoc in the six-yard box.
Not since September 28 when they lost to West Bromwich Albion had North End been beaten on home turf, this only a third Deepdale reverse in the Championship this season.
The positives to take from defeat were the performances of substitutes Jordan Storey and Ryan Ledson.
Storey came on in the first half when Ben Davies added his name to the casualty list with a hamstring injury, Ledson's introduction as tactical one at half-time.
Both made an impact, Storey looking assured at the back and Ledson prompting play from a holding midfield role.
North End's side had shown three changes to the one beaten at Sheffield Wednesday last Saturday.
Ben Pearson started a four-game suspension, Louis Moult was ruled out through injury and Darnell Fisher dropped down to the bench.
Alan Browne, Tom Clarke and Graham Burke came into the side, this Burke's first start since September 1.
An early chance came about when Paul Gallagher's free-kick into the box was won in the air by Paul Huntington.
The ball bounced down into the path of Burke whose shot was blocked, Huntington's follow-up also hitting a defender.
Lukas Nmecha sent a header wide of the near post after meeting Tom Barkhuizen's cross from the left.
While seeing plenty of the ball in the opening 20 minutes, much of North End's play came in front of their visitors' defence which stayed tight and rigid.
With 25 minutes played, Burke hit a volley into the ground from Andrews Hughes' cross.
It was blocked and cleared out of the box as far as Gallagher, the midfielder's shot touched wide by keeper David Marshall.
Hull went ahead in the 28th minute, Grosicki's pass releasing Stephen Kingsley on the overlap down the left.
Kingsely lifted a fine cross into the box, Irvine arriving late in the middle to power a header into the roof of the net.
North End suffered an injury blow when Ben Davies limped iff in the 34th minute with what looked a like a hamstring injury, Jordan Storey replacing him.
Browne hit a volley from the edge of the box straight at the keeper after Burke has chested the ball down into his box.
It needed a fine save from Declan Rudd four minutes before the interval to prevent Hull extending their lead.
Jarrod Bowen's corner from the right found its way through to Jordy de Wijs at the far post, the defender's header well parried by Rudd at close quarters with Storey hooking the loose ball clear.
If their first-half show had been tepid to say the least, Preston started the second all fired-up and were level inside two minutes of the re-start.
The equaliser was a moment of quality, Browne collecting possession 25 yards out and rifling a right-foot shot into the top corner of the net.
It sparked a period if pressure from North End in which they fashioned three decent chances in the space of a few minutes.
Clarke's free-kick from his own half sailed over the Hull defence, Gallagher stealing in behind to meet it with a header which dropped inches wide.
Barkhuizen cut into the box and hit a low curling right-foot shot which Marshall dived to push past the post, then Nmecha met Clarke's with a bicycle kick which the keeper held.
PNE supporters held their breath in the 67th minute when Irvine got clear in the box, Huntington's sliding challenge taking the ball off the Australian who appealed loudly for a penalty.
Referee Scott Duncan waved play on though, deeming Huntington had won the ball cleanly.
Rudd saved well low down by the far post to push Todd Kane's shot behind, Grosicki's cross having travelled across the box to find the ex-PNE loanee.
Hull regained the lead in the 80th minute as a spell of pressure which had been building-up, paid dividends.
Grosicki's corner from the left was played deep to the far post, causing havoc in the six-yard box.
A first attempt on goal by Tommy Elphick was blocked on the line before Irvine headed it over the line from close range.
North End couldn't fashion a response, seeing plenty of the ball late on but without seriously testing the Hull defence which held firm to record a third successive victory for the visitors.
PNE: Rudd, Clarke (Fisher 82), Huntington, Davies (Storey 34), Hughes, Gallagher, Johnson, Barkhuizen, Browne, Burke (Ledson 46), Nmecha. Subs (not used): Woods, Simpson, Walker, Crowe.
Hull: Marshall, Kane, Elphick, De Wijs, Kingsley, Stewart, Henriksen, Bowen (Lichaj 90), Irvine, Grosicki (Burke 90), Campbell (Martin 85) Subs (not used): Dicko, Batty, McKenzie, Long.
Referee: Scott Duncan (Northumberland)
Attendance: 14,026 (604 away)