The behind closed doors clash went the full distance, finishing 1-1 after 90 minutes - Daniel Johnson' s penalty nine minutes into the second half equalising a first-half opener from Isaak Davies.
Cardiff won it with a goal in the 116th minute, Mark Harris finishing well on the counter-attack from fellow substitute Tom Sang's cross.
The zip of Ryan Lowe's first two games in charge was missing from North End's play for large parts in South Wales.
It wasn't a classic game by any stretch of the imagination, two Championship teams slogging it out.
A penalty shoot out looked the most likely outcome until the home side took advantage of some poor Preston defending to get the winner.
The North End starting XI had shown four changes to the side which beat Stoke last Monday, Greg Cunningham Ryan Ledson, Ali McCann and Sean Maguire coming into the side.
Alan Browne, Ben Whiteman and Ched Evans dropped to the bench, with injury ruling Andrew Hughes out.
PNE made the brighter start in the eerie stadium, Josh Earl seeing a shot blocked at close quarters for a corner after he had picked out with a diagonal ball into the box.
At the other end Marlon Pack's shot from 20 yards went too high, the chance falling to him after PNE had cleared a corner out of the box.
North End skipper Johnson dragged a shot wide of the near post from the right-hand corner of the box.
Cardiff squandered a great chance to go in front in the 25th minute, Rubin Colwill's pass sending Davies behind the Preston defence and through on goal.
With just Daniel Iversen to beat, Davies pulled his shot wide of the near post.
Brad Potts got on the end of a Cunningham cross just after the half-hour mark but his header from 14 yards went well wide of the target.
Bluebirds goalkeeper Dillon Phillips had to scramble across his six-yard box to stop Sean Morrison's back pass beating him, Phillips stretching out a foot to halt it and clear.
North End fell behind three minutes before half-time to a soft goal.
When a ball was played down the home side's left channel, Sepp van den Berg got across and looked favourite to get it.
But Davies nicked it just before him and set off towards the box.
He cut inside across the face of the box, Patrick Bauer hesitated making a challenge and that gave Davies the chance to shoot, his low right-foot effort going through Iversen's legs into the net.
North End were level within eight minutes of the start of the second half via the penalty spot.
Ledson slid a pass into the box for Maguire to chase, Sean Morrison sliding in with a clumsy challenge which took Maguire to the floor.
Referee Andy Woolmer pointed to the spot after a couple of moments hesitation, just giving himself a bit of thinking time to make sure Maguire hadn't gone down too quickly.
Johnson was his normal composed self with the penalty, taking his time placing it on the spot before sending the keeper the wrong way with a good finish into the bottom left-hand corner of the net.
The visitors made their first change soon after the goal, Scott Sinclair replacing Riis up front.
In the 63rd minute, McCann's run towards the box was halted by Perry Ng's foul, one which earned the Cardiff wing-back a yellow card.
Johnson tapped the free-kick sideways to Ledson whose shot bounced against the home side's wall and away to safety.
A chance fell Maguire's way when he dropped deep to receive the ball and turned to have a run at goal. His curling shot from the edge of the box drifted wide of the target.
North End made a double change in midfield with 10 minutes remaining, Josh Harrop and Whiteman replacing McCann and Ledson.
It was Harrop's first time on the pitch in a PNE shirt since Boxing Day 2020.
With 90 minutes unable to separate the sides, the tie moved into extra-time.
Two minutes into the first period, Potts' cross from the right travelled across the box to find Earl at the far post but he shot wide.
In the 100th minute, Haris came inside off the left-wing and curled a shot goalwards, Iversen diving to push it past the far post.
Johnson pulled up with cramp towards the end of the first period of extra-time, Browne coming off the bench to replace him.
Cunningham put a header just wide of the far post from Whiteman's corner in the second period, the game's tempo having slowed .
Cardiff's winner came in the 116th minute, poor defending allowing Sang to get behind the PNE defence on the left.
With North End caught two against four, Sang's cross found its way through to Harris who picked his spot with a low finish across Iversen.
In stoppage-time of extra-time, PNE claimed they should have had a penalty - with replays backing it up.
Curtis Nelson handled the ball in the box but Mr Woolmer gave the home side a free-kick, citing that substitute Ched Evans had pushed Nelson before the contact with the ball.
It looked the wrong decision with the referee just a few yards from it.
Cardiff: Phillips, Morrison, Nelson, Brown (Harris 68), Ng, Vaulks, Pack (Sang 100), Bagan, Davies (Evans 90), Colwill (Wintle 75), Collins. Subs (not used): Ratcliffe, McGuinness, Flint, King, Patten..
PNE: Iversen, van den Berg, Bauer, Cunningham, Ledson (Whiteman 80), Potts, McCann (Harrop 80), Johnson (Browne 104), Earl, Maguire (Evans 93), Riis (Sinclair 58). Subs(not used): Hudson, Storey, Lindsay, Rafferty.
Referee: Andy Woolmer (Northants)