The striker volleyed home his ninth goal of the campaign in the 58th minute, meeting a fine cross from Callum Robinson.
It gave North End their third victory on the bounce and stretched their unbeaten run to six matches.
The first-half had been a keenly-fought affair but without too many chances of note and quality, Paul Gallagher going closest with a free-kick which hit the top of the bar.
PNE got on top in the second half and had the momentum when Hugill struck.
While they had defending to do after taking the lead, there was little from the Blades attack to worry Chris Maxwell.
Alex Neil had made one change to the side which had started last week's win at Burton, Daniel Johnson replacing Alan Browne.
North End lined-up in a 4-4-2 system to start with, strikers Hugill and Tom Barkhuizen pulling very wide to pin back United's defence.
The midfield had a diamond shape, Ben Pearson playing at the base of it, Gallagher and Johnson in front of him, with Robinson at the point.
A slip at the back let in the Blades for the first chance of the game inside the first minute, Leon Clarke getting room down the right hand side of the box, Ben Davies sliding across to block the striker's shot and take it behind for a corner.
In the sixth minute, a cross from the left-wing travelled across to the far post where Jack O'Connell looped a header on to the top of the net.
Robinson, lively in the opening stages, saw a shot from 25 yards fly over the bar.
Soon after, a mazy run carried Robinson into the box but he was tackled before being able to pull the trigger.
The same player went close with 18 minutes played, bursting into the box and hitting a shot which United goalkeeper Simon Moore tipped over the bar.
Chris Basham tried his luck with a low shot from outside the box which trickled through to Maxwell.
North End lost Darnell Fisher in the 27th minute, the left-back limping off after receiving treatment a few minutes earlier - he was replaced by Kevin O'Connor.
Just before that, Neil had switched to a 4-3-3 formation, Hugill playing more centrally and flanked by Barkhuizen and Robinson.
Their best of the first half came five minutes before the interval after Hugill was fouled a couple of yards outside the box.
Johnson rolled the free-kick short to Gallagher whose right-foot effort beat the wall and hit the bar before going over.
In the 53rd minute, Preston broke at speed from the edge of their own box, Gallagher's pass finding Barkhuizen who swept into the visitors half before finding Robinson to his left.
Robinson took the ball into the box but dragged a low shot across the face of goal and wide of the far post.
North End pushed on from there, applying a spell of pressure and making the breakthrough in the 58th minute.
It was Robinson with the assist, sending in a peach of a cross to find Hugill in the six-yard box, the striker cushioning a volley into the net.
After the goal, PNE had some defending to do as United took off a defender to put on an extra attacker in Clayton Donaldson.
Neil made a double substitution in the 77th minute, Browne and Josh Harrop coming off the bench to replace Gallagher and Robinson.
Maxwell had to dash off his line to reach a through ball ahead of Donaldson, good awareness shown by the keeper.
Harrop blazed a shot over the bar from 25 yards in the 83rd minute as the play opened up in front of him, a calmer head required in the circumstances.
Hugill went so close to a second goal in the 89th minute, taking the ball on his chest with his back to goal, turning and hitting a right-foot shot from 20 yards which the keeper dived to push behind.
PNE: Maxwell, Clarke, Huntington, Davies, Fisher (O'Connor 27), Pearson, Gallagher (Browne 77), Barkhuizen, Johnson, Robinson (Harrop 77), Hugill. Subs (not used): Boyle, Horgan, Mavididi, Rudd.
Sheffield United: Moore, Carter-Vickers (Donaldson 68), Stearman, O'Connell, Baldock (Lafferty 58)), Lundstram, Carruthers (Slater 74), Stevens, Sharp, Clarke. Subs (not used): Wright, Lavery, Henegan, Blackman.
Referee: Tim Robinson (West Sussex)
Attendance: 15,202 (3,850 away)