The visitors had an early chance when Stephen Elliott broke into the box but his touch let him down at the vital time and he was unable to get in a shot.
It was Scunthorpe who took charge after Grant McCann fired them in front in the 12th minute from a cross by Paul Hayes.
Striker Gary Hooper was a thorn in the side of the Preston defence all night.
He was denied a goal by a clearance off the line from midfield man Chris Sedgwick.
But Hooper did strike in the 43rd minute when he applied the finishing touch to another excellent cross from Hayes.
Preston started the second half strongly looking to try and get back into the game but found little joy against a solid home defence.
It was Scunthorpe who made it 3-0 after 53 minutes when Michael O'Connor won the ball in midfield and threaded it through for Hooper to race into the box and beat keeper Andy Lonergan with his second goal of the game.
Preston had a glimmer of hope six minutes later when striker Jon Parkin crashed a shot home from close range after the home defence had failed to clear a corner.
But it proved little more than a consolation as hard-working Scunthorpe stood firm.
It was the home side who might have added to the score in the closing stages when Hooper again got clear into the box only to be denied by a good save from Lonergan.
Preston brought on strikers Chris Brown and Neil Mellor in the closing stages but they failed to have the impact manager Alan Irvine was looking for.