North End were 3-1 winners at Bramall Lane that chilly February evening after coming from a goal down.
It was game that proved to be a catalyst for the Lilywhites’ season, with Simon Grayson’s side having struggled for form leading into the contest.
In their remaining 19 League One games of the 2014/15 season they lost just once, on the last day against Colchester United, before securing promotion through the play-offs at Wembley.
PNE and the Blades had drawn 1-1 at Deepdale initially in the fourth-round tie, Paul Gallagher and Diego De Girolamo finding the net but there was nothing to separate the promotion-chasing pair, requiring a replay.
Jamie Murphy gave hosts United a half-time lead against their League One rivals in the second tie.
ButGallagher, who scored a stunning free-kick in the first tie at Deepdale, did it again to equalise.
Paul Huntington then headed in Scott Laird’s corner before Gallagher converted a penalty to secure victory.
Preston were good value for their victory against a Sheffield United side who were FA Cup semi-finalists the season prior.
Nigel Clough’s team were lucky not to go behind when PNE striker Kevin Davies – a boyhood Blades fan – chipped against the post after latching on to Chris Basham’s weak back header.
Chances each for Tom Clarke and Laird, both headers, were repelled by the Mark Howard in the Blades’ goal.
Preston arrived at Bramall Lane without a win in seven matches, and might have been forgiven if their confidence had dipped after conceding a soft goal seven minutes before the break.
Murphy collected Michael Doyle’s pass and rolled a shot under Preston goalkeeper Thorsten Stuckmann, who probably should have saved it.
North End’s second-half fightback, though, was emphatic.
Home keeper Howard made a superb double save to stop Laird and Chris Humphrey, shortly before on-loan Leicester man Gallagher hit an unstoppable free-kick into the top corner on 63 minutes.
The midfielder netted his fourth and fifth FA Cup goals of the season on the night, having become PNE’s first ever loan player to score a hat-trick with a treble against Barnet in the first round two years prior.
He finished the competitions joint top scorer in 2015 on five.
The visitors were in front six minutes later, as Huntington headed in Laird’s corner for his second goal in two matches.
Gallagher got his second of the night to make sure of the win in the 73rd minute by drilling a penalty into the corner of the net after Humphrey was tripped.
North End secured the win against cup specialists Sheffield United, who suffered just their third defeat in their last 18 FA Cup matches, and set up the huge clash with Manchester United that would sell out at Deepdale.
On the win, PNE boss Grayson said: “It’s been a disappointing few weeks for us but tonight is an excellent result.
“There was a massive incentive tonight to play Manchester United, and it brought out the best in us.
“We had to be focused tonight, because we know how good Sheffield United are.
“They have done fantastically well in the cups.
“We had to be at it, and from the first whistle we were really good and dominated, and they scored against the run of play.
“But we kept our belief going.”