Ugo Ehiogu scored the winner to keep Sheffield United in touch with the Championship leaders and hand Preston their sixth defeat in seven games.
Preston dominated the first half but The Blades stepped up a gear after the restart and were soon rewarded.
Veteran centre-back Ehiogu rifled the ball into the back of the net from eight yards after the visitors failed to clear a free-kick from Brian Howard.
And it proved enough to seal all three points for the hosts.
Sheffield United manager Kevin Blackwell:
"We've had a long, hard week with three games in six days, but the lads have given me everything they have got and that's all I can ask for.
"At this part of the season it's about getting results and then the football starts to flow.
"We are jockeying for position and if we can up there around Christmas time then we'll be in a good position to strike."
Preston manager Alan Irvine:
"I think that it was very harsh and it's a huge disappointment. We did enough to get something. Unfortunately things have turned the wrong way in recent weeks after we did so well from probably January onwards.
"But nobody has hammered us and the players are exasperated. We shot ourselves in the foot by not getting a goal in the first half."
Sheff Utd: Kenny, Naughton, Morgan, Ehiogu, Naysmith (Jihai 46), Webber (Halford 78), Howard, Spring, Quinn, Beattie (Sharp 87), Stokes.
Subs Not Used: Cotterill, Montgomery.
Booked: Naughton, Kenny, Howard.
Goals: Ehiogu 50.
Preston: Lonergan, Jones, Mawene, St. Ledger, McEveley, Sedgwick (Whaley 86), McKenna, Nicholson, Wallace, Parkin, Elliott (Mellor 60).
Subs Not Used: Jarrett, Nolan, Chris Neal.
Booked: Nicholson, Parkin, Jones.
Att: 24,445
Ref: Dean Whitestone (Northamptonshire).
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