Preston goalkeeper Andy Lonergan saved after three minutes from Paul Hayes' back post shot from Gary Hooper's low cross. He came out quickly to close the ball down and conceded a corner.
In the 17th minute, Sean St Ledger's pass from the back found Preston striker Jon Parkin just outside the Scunthorpe box. Parkin laid the ball into the path of Paul Coutts, whose left-foot shot deflected off a defender and spun into the arms of keeper Joe Murphy.
Preston right-back Billy Jones surged into the box and crossed to Keith Treacy who hit an 18-yard right-foot volley into the ground which was easy for Murphy after 19 minutes.
Preston's top scorer Parkin scored his 13th goal of the season and first goal since the end of February with a six-yard low shot into the bottom left in the 28th minute, from Treacy's left-foot cross.
Parkin had an effort saved from a Treacy cross after 33 minutes and Lonergan conceded a corner with a diving one-handed save from a 20-yard Grant McCann shot a minute later.
After 38 minutes Murphy pushed Parkin's low left-foot shot around the near post for a left-wing corner after he had played a one-two with Coutts.
Preston captain Callum Davidson found 19-year-old full debutant Danny Mayor down the left. He beat the full-back and cut inside and hit a right-foot shot which Murphy saved low down to his right at the foot of the post just before half-time.
Preston striker Neil Mellor replaced Adam Barton and Josh Wright replaced Martyn Woolford at half-time.
Matthew Sparrow's 20-yard shot was saved and Treacy had a deflected shot which Murphy saved down to his right turning the ball away after 53 minutes.
St Ledger's short back pass put Garry Thompson clear through on goal and he equalised in the 64th minute from inside the area low into the middle of the goal.
Mellor's shot and Parkin's header were saved.
Thompson down the left made it 2-1 to Scunthorpe in the 72nd minute from inside the box to the bottom right corner of the goal in off the post from McCann's assist.
Preston striker Chris Brown replaced Parkin in the 73rd minute and Michael O'Connor replaced Hooper in the 75th minute.
Jones equalised in the 86th minute with a close-range header after Murphy parried Mellor's header.
Seconds after being named as man-of-the-match Irishman Treacy made it 3-2 to Preston in the 93rd minute.
He picked the ball up on the right, cut inside his marker, tipped the ball one more time before hitting a stunning curling effort across goal, beyond the keeper and into the top left corner.