Second half goals from Scott Sinclair, Emil Riis and Brad Potts saw table-topping Reading beaten for the first time this campaign in an excellent away performance.
Here are six talking points from the game...
1. PNE march on away from home.
North End went into Wednesday's game against Reading as the best side in the division away from home, they went up against the league leaders who were yet to be beaten at home and returned to PR1 with the spoils.
Reading were the side to beat in the division and PNE did exactly that.
They came out of the blocks really well and survived when Reading came into the game as the first half wore on.
The second half was everything good about PNE away from home at the moment, they were clinical and quick on the break.
Emil Riis was a great focal point to work through and they used him to perfection.
That puts the Lilywhites up to 12th in the table, four points away from the play-offs as it stands - without taking a single point from a home game.
The home form certainly needs to improve but it's been so near perfect on their travels so far.
2. Defence doing their bit.
In a 3-0 win you often look at the forwards that did the damage on the night but the only reason they were able to do their job is because the lads at the back were doing theirs.
In what you would have to call a makeshift defence of sorts, Paul Huntington came in to the heart of the defence to partner Jordan Storey - neither first choice generally.
That is no disrespect to the pair, who are usually seen behind Ben Davies and Patrick Bauer in the pecking order.
'Hunts' and Storey were immense at the heart of the defence, especially given how sporadic their game time can get.
Partner that with Declan Rudd making big saves at key moments and being able to punt the ball with accuracy right down to the opponents' box and it's a very good defensive core.
Storey had one shaky moment in the game, cheaply giving away possession on the edge of his half for Lucas Joao to run through on goal.
The 23-year-old made up the ground and executed a perfect slide tackle to prevent the striker from even being able to pull the trigger.
Huntington alongside would seemingly take a bullet for Preston North End, came in for praise from his manager and plenty of PNE fans too after the game.
3. Riis off the mark.
It was always a case of if and not when with the new Dane in PR1 but it happened on Wednesday, Emil Riis hit the back of the net for PNE.
Despite creating for his teammates regularly and having a few chances for himself, it took Riis seven games to bag for the first time, though not full games.
It was never in any doubt though, finally getting what he has deserved with a cool finish after being played in behind by Ryan Ledson.
Riis showed all facets of his game at the Madejski Stadium, winning another penalty with his pace in behind, bullying the Reading defenders and causing a nuisance but also having the deftness of touch to lay the ball off simply or with flicks.
Hopefully that goal will have lit the touch paper for the 22-year-old and his good play will be rewarded with more goals.
4. Neil in?
After highlighting the discontent within the fanbase after the weekend's defeat it is also worth highlighting how quick football can change.
Though those that thought Neil's time is up won't have changed their mind over one result, there is much more of the fans questioning their views being heard now.
It's often said that you are only as good as your last game and so the mood will rightly be very good around the team until the weekend and whatever happens against Rotherham United, but the performance against Reading again goes to show why there is quality in the Scot's stewardship.
The home form hasn't been addressed and isn't acceptable, that is for all to see and the manager himself is the first to say that, but having turned both the title favourites and the league leaders over in their back yard, surely there are enough positives to direct the emotion instead to supporting the team - albeit from afar - rather than calling for their boss' head?
For the moment at least, Alex Neil will get some reprieve from a minority - as shown via Twitter poll - of the PNE fanbase.
5. Daniel Johnson misses a penalty. No, really.
When you think you've seen everything in 2020, as a president calls an election a fraud and announces himself winner in states that haven't even finished counting the votes yet and as we enter a second lockdown of a global pandemic distancing us from family, friend and hobbies - it goes one further.
Daniel Johnson misses a penalty for PNE.
As Alex Neil has said in the past, when North End's no.11, or Paul Gallagher, step up to take a penalty the opposition would be just as well going back to the halfway line to restart the game.
That would have been true up until Wednesday when Rafael Cabral made a save diving to his right with his legs.
Johnson's usual confident routine would have had all viewers believing the usual would happen but instead he placed the ball just right of centre and the Royals' stopper made the all-important block.
All-important until Scott Sinclair opened the scoring.
It can instead now be a novelty side note on the night, that the soon-to-be Jamaican international was unsuccessful from 12 yards and his perfect record in 90 minutes is gone.
Credit to him and his teammates for putting that disappointment behind them and it not effecting their performances, even without that chance being taken they still ran out comfortable and deserving winners on the night.
6. We are the Millers.
Attention now quickly turns to Saturday's game against Rotherham United as there is no let up in PNE's Championship fixture list.
The Millers have won one of their home games so far this season and lost in the week hosting Luton Town.
United have been tipped to return to League One having sealed promotion last season and Preston will travel their still at the top of the away form table.
It is the last game before another international break and winning prior to the last one kept spirits up throughout the pause in domestic action for Neil's men.
It may prove a different prospect for the Lilytwhites however, Reading were flying high at the top of the division and were prepared to take the game to PNE whenever they could.
It might be that Rotherham take a more pragmatic approach and North End may have to break them down and play through them a little more than they were forced to against the Royals on Wednesday.
Rotation is an option for Neil, with Tom Barkhuizen coming off the bench to set up Potts' late goal, and with six changes last time out he's clearly not afraid to shake things up and surprise.
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