It was a third loss on the bounce and fourth in five games, piling the pressure on Alex Neil.
Just three times have North End won in 2021 and they must now anxiously look over their shoulders at what is below.
The cushion between themselves and the bottom three is down to nine points, 22nd place Rotherham having four games in hand.
What must be born in mind too is PNE's three games after the international break are against Norwich, Swansea and Brentford - three of the current top four.
Luton's winner at the end of a poor spectacle came in the 83rd minute.
Kiernan Dewsbury-Hall's close-range effort was superbly kept out by Daniel Iversen.
But substitute James Collins turned the rebound back from beyond the far post, the ball touching off Iversen on the way over the line.
If that does go down as an own goal it would be mightily unlucky for the goalkeeper who had been Preston's best player. Should Collins get it, that was his fourth goal against PNE this season following a hat-trick at Kenilworth Road in December.
North End again lacked attacking ideas, their first shot on target coming from Ched Evans in the 70th minute.
The North End side had shown five changes to the one which started last Tuesday night's 2-0 defeat at Middlesbrough.
Joe Rafferty, Daniel Johnson, Ryan Ledson, Anthony Gordon and Ben Whiteman returned, with Alan Browne, Andrew Hughes, Paul Gallagher, Tom Barkhuizen and Brad Potts dropping out.
Browne served the first game of a three-match suspension, with Hughes out injured.
The first half was very much a battle of attrition, the ball spending a lot of time in the air.
Luton had the better of the chances in the opening 45 minutes, the first in the 11th minute being a shot from Elijah Adebayo which caught Jordan Storey's boot as he challenged and deflected behind.
North End's one chance of the first period was Sepp van den Berg's header from a Ledson corner which went over the bar.
There was a scare after half an hour when Liam Lindsay dwelt too long on the ball rather than clear, Harry Cornick taking it off him and getting clear, Joe Rafferty covering well to block.
A shot from Pelly Ruddock Mpanzu hit Lindsay on the header and flew behind for a corner, while Iversen got down at the near post to smother Adebayo's attempted cut-back from the byline.
Still limping after being bundled over gathering a corner, Iversen pulled off a fine save in the 45th minute.
James Bree drove in a low angled shot from outside the box which caught a deflection, the Danish goalkeeper diving low to his right to push it past the far post.
Scott Sinclair, who had been on the periphery of the game, produced a spark in the 55th minute, dribbling into the box from the right-wing and hitting a low shot which Kal Naismith blocked.
Iversen pulled off another save at the other end two minutes later. Bree's cross from the right found Adebajo whose header back across goal was parried by the keeper.
Sean Maguire and Barkhuizen came off the bench in the 67th minute to replace wingers Sinclair and Gordon.
With five minutes, Maguire slipped a pass through to find Evans in the six-yard box to the left of goal, Hatters goalkeeper Simon Sluga blocking bravely at Evans' feet, the ball going out for a corner.
Luton's winner came seven minutes from time, Bree's cross from the right finding Kiernan Dewsbury-Hall close in.
His effort was superbly saved at point-blank range by Iversen but Collins turned the rebound home from beyond the far post - it touching off Iversen and over the line.
The closest chance to an equaliser came in the 87th minute. Barkhuizen's long throw found it Lindsay who flicked a back header towards goal, Sluga diving to tip it away.
Maguire was first to the rebound but lifted a shot over the bar.
PNE: Iversen, van den Berg, Storey, Lindsay, Rafferty, Whiteman, Ledson (Gallagher 85), Sinclair, (Maguire 67) Johnson (Bodin 81), Gordon (Barkhuizen 67), Evans (Potts 81). Subs (not used): Riis, Molumby, Huntington, Ripley.
Luton: Sluga, Pearson, Rea, Naismith, Bree, Mpanzu, Tunnicliffe (Ince 70), Dewsbury-Hall, Clark, Cornick (Collins 76), Adebayo (Nombe 76) Subs (not used): Cranie, Berry, Lockyer, Lualua,, Morrell, Shea.
Referee: Thomas Bramall (South Yorkshire)
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