A brilliant 65th minute penalty save by goalkeeper Joe Murphy secured Scunthorpe a third successive home win.
He went full-length to turn away a well-struck spot-kick from Preston skipper Kevin Nicholls.
It heaped more misery on the visitors, who had been reduced to ten men just three minutes earlier when young striker Andy Carroll was shown a straight red card for violent conduct after kicking out at Andy Butler.
Preston started confidently moving the ball about well, but it was Scunthorpe who opened the scoring in the 24th minute when skipper Andrew Crosby scored in his second successive home game after heading home from a corner by Kevan Hurst.
Scunthorpe's leading marksman Martin Paterson was always a handful and twice he was denied a fifth goal of the season by good saves from keeper Andy Lonergan.
At the opposite end, Murphy was called into action for the home side when he went full-stretch to turn away a stinging drive from midfield man Darren Carter.
Murphy also did well to beat away a shot from striker Patrick Agyemang who had broke clear into the box.
The visitors were back on level terms in the 44th minute when centre-back Youl Mawene out-jumped the home defence to head home a free-kick from Nicholls.
But Scunthorpe were back in front four minutes into the second half when Paterson set up an opening for Paul Hayes to force a close-range shot past Lonergan for his first goal since returning to the club this summer from Barnsley.
Paterson had a chance to wrap the game up when he broke free through the middle late in the game but delayed his shot and saw it blocked away with the goal seemingly at his mercy.
Preston threw everything forward in search of a last gasp equaliser but the nearest they came was when substitute Brett Ormerod curled a shot over from the edge of the box.
The result leaves Preston struggling near the foot of the table and still searching for the form that took them into the play-offs last season.