PNE 1 Manchester United 3
Laird pounced just after the break to fire low into the bottom right hand corner of David De Gea’s goal, via a deflection to send the capacity crowd wild.
However, Herrera’s hotly disputed equaliser, Fellaini’s close range drive and Rooney’s penalty, after Thorsten Stuckmann was adjudged to have brought down the England skipper, gave the Red Devils a 3-1 win.
It was a back three for the Lilywhites when the teams were announced; with Garner and Kevin Davies the two men up front.
The sense of anticipation rose around Deepdale as the draw pitted the winners of the tie at home to Cup holders Arsenal.
The Lilywhites held their own in a cagey opening half, Joe Garner scuffing an effort wide from Neil Kilkenny’s ball into him 25 yards out and England and United skipper Wayne Rooney mis-controlling as he seemed destined to bear down on Thorsten Stuckmann’s goal.
The closest either side came in the opening half came on the 15 minutes mark when the visitors were awarded a free kick 28 yards out in a right hand channel after foul by Wright on Falcao. Angel Di Maria stepped up, but put the ball wide of the right hand upright.
Just before the hour mark a Paul Gallagher free kick from the left was swung in and Joe Garner rose highest to head over the bar under a lot of pressure from Marcos Rojo.
The deadlock was broken two minutes into the second half. North End broke down the left and Scott Laird was fed by Gallagher and drove into the box firing hard and low, the ball taking a ricochet under David De Gea and into the bottom right hand corner.
North End almost had a second five minutes later as a Paul Gallagher free kick from the right found its way to the back post and Tom Clarke under severe pressure almost volleyed home, eventually the ball going out for a goal kick at the back post.
Just after the hour mark and Joe Garner found himself in space in the box; Humphrey found him with a clever ball in and the 14-goal frontman got his header on target, but David De Gea got down low to save.
The visitors, however, drew level on 65 minutes. Ander Herrera was the goalscorer, steering the ball in off the left hand post from the edge of the box, however, North End were left angry as they felt Stuckmann was left unsighted by Wayne Rooney stood offside in the six yard box.
It was now end to end and Joe Garner was brought down by Marcos Rojo, allowing Paul Gallaghe to curl a beautiful free kick that was only an inch over the bar and onto the roof of De Gea’s goal.
But it was the visitors who grabbed the third goal of the game. Antonio Valencia got down the right and drilled a cross to the back post where Marouane Fellaini headed down, Stuckmann making a save, but the ball came back to the big-haired Belgian who fired hard into the top right hand corner from the edge of the six yard box.
Simon Grayson made aw triple change with 15 minutes left, Scott Wiseman, Kyel Reid and the returning Callum Robinson introduced for Kilkenny, Kevin Davies and Bailey Wright.
With ten minutes left North End had two great chances to draw level. Joe Garner was found by Laird from the left and h had Humphrey wide to his right but tried a back heel which came out to Kyel Reid, whose shot was inches wide of the left hand post with De Gea beaten.
Callum Robinson tested De Gea from 25 yards after finding some space in the middle of the United half; his pace evident from the outset of his introduction once again.
And with three minutes left Rooney went down after racing through, Stuckmann sliding out. Referee Phil Dowd awarded a penalty and the England captain stepped up and fired into the top right hand corner to guarantee the Red Devils a tie with Arsenal in the quarter-finals.
Scott Laird thought he had a second in injury-time when his flashing header at the near post from Paul Gallagher's corner was goalbound, but Herrera did a brilliant job to keep it out on the line and North End'sd adventure in the 2015 FA Cup was over.
PNE line-up: Stuckmann, Humphrey, Laird, Clarke (c), Huntington, Wright (Wiseman, 75), Welsh, Kilkenny (Reid, 75), Garner, K Davies (Robinson, 75), Gallagher. Subs not used: Hudson, King, Brownhill, Ebanks-Blake.
Manchester United line-up: De Gea, Shaw, Rojo, Di Maria, Falcao (Young, 60), Rooney (c), Smalling, Blind, Herrera, Valencia, Fellani. Subs not used: Valdes, Evans, Mata, Januzaj, McNair, Wilson.
Attendance: 21,348 (4,668 away fans)
Referee: Mr P Dowd