All the significant action came in a dramatic first half at Elland Road.
Daniel Johnson put PNE in front from the penalty spot after Louis Moult had been fouled just 43 seconds in.
But it looked like potentially being a long night when Ryan Ledson was shown a straight red just before the half hour for a wild challenge on Lewis Baker.
That didn’t prove to be the case though.
Preston North End boss provides injury update on Manchester United loanee and addresses specualtion linking them to another Red Devils youngster
Manchester United youngster being tested by Preston North End on a 'daily basis' after sparkling debut
The best fans photos from Preston North End's 4-1 win over Huddersfield Town in the Carabao Cup.
Wigan remain Championship relegation candidates but bookies' odds drift for Preston North End and Blackpool
Preston North End debutant talks making the step up, learning from Robbie Brady and Alvaro Fernandez and this only being the beginning
Brandon Barker scored a stunning second on the stroke of half-time with Alex Neil’s men then producing a resolute defensive display after the break to frustrate their more fancied hosts.
The PNE boss had made seven changes to the side that lost at Derby last time out in the Championship while his Leeds counterpart Marcelo Bielsa made nine alterations.
The visitors made a remarkable start, winning a penalty on their first attack.
PNE won the ball back high up the pitch, a feature of their play in West Yorkshire, with Moult receiving the ball in the box and taking a touch before being felled by Conor Shaughnessy.
The clock had ticked along to one-and-a-half minutes by the time Johnson stepped up and sent Jamal Blackman the wrong way from 12 yards.
The Lilywhites were swarming all over their hosts and Tom Barkhuizen nearly made it two in just the third minute with his shot from 20 yards deflected wide.
As the early Championship leaders were rocked Moult came close to robbing goalkeeper Blackman on the edge of his own area, the PNE front man nicking the ball only for Leeds to just about scramble clear eight minutes in.
The hosts grew into the game though, Tyler Roberts shooting wide from a good position before Chris Maxwell produced a sharp save to help Jamie Shackleton’s shot from a drilled Stuart Dallas cross over the bar on the quarter hour.
An open cup tie then seemingly turned firmly in the hosts’ favour just before the half hour mark.
Ledson went in to a 50-50 challenge with Baker and despite having a good chance of winning the ball followed through with an ugly, high tackle that left referee Tony Harrington with no choice but to send him off.
As PNE tried to sure things up the hosts sensed an opportunity.
One cross into the box was half-punched clear by Maxwell with Ben Davies in the right place to block Pontus Jansson’s returning header on the line.
Maxwell was then in action again producing a sharp low save to keep out Bamford’s swerving shot from 20 yards 10 minutes before the interval.
Johnson then had a sight of goal, half-volleying over the bar before Jack Harrison twisted and turned at the other end but couldn’t trouble Maxwell.
Then, out of nothing, North End doubled their advantage on the stroke of half-time.
Barker took control of the ball 30 yards from his own goal and drove over halfway, beating three men before firing home a stunning left-footed effort from just inside the area.
Bamford went close either side of the interval, Bielsa making a double change at the break in a bid to get his side back into the game.
Chances were few and far between though, Ben Davies and Jordan Storey proving a formidable partnership at the back.
Johnson did see one tame shot saved before he and Barker were removed with 20 minutes to play with Ben Pearson and Alan Browne brought on to sure things up.
Almost immediately after their introduction, Leeds had a sight of goal, Maxwell’s punch falling into the path of substitute Samuel Saiz who could only slice his effort wide.
Leeds huffed and puffed but despite the introduction of some of the players who have helped them to the top of the early Championship table, they lacked quality in the final third, Baker and Ezgjan Alioski both firing over and Maxwell saving from Saiz.
For PNE, it was a performance that should really get them going again after two disappointing defeats in the Championship.
Leeds: Blackman, Pearce, Shaughnessy (Saiz 46), Jansson, Shackleton (Klich 46), Baker, Phillips, Harrison, Dallas (capt), Roberts (Alioski 60), Bamford. Subs not used: Huffer, Douglas, Ayling, Roofe.
PNE: Maxwell, Fisher, Storey, Davies (capt), Earl, Ledson, Johnson (Pearson 70), Barkhuizen, Harrop, Barker (Browne 70), Moult (Nmecha 74). Subs not used Rudd, Hughes, Huntington, Burke.
Referee: Tony Harrington