For long spells Cambridge had matched the home side and were probably unlucky to fall behind before the interval.
However it was substitute Cleveland Taylor who changed the pace of the game as introduced with 25 minutes left, he scored two great goals and skipper Andrew Crosby was a real inspiration at the back.
Cambridge now face a mountainous job if they are to escape the drop, and the manager Steve Thompson has a difficult task in motivating his players for the final three games.
Tes Bramble was always in the thick of the action while Daniel Chillingworth was rather unlucky not to get on the scoresheet.
The opening stages saw Cambridge setting the pace, with Bramble involved in a sweeping move on the right which ended when Ashley Nicholls, completely unmarked, drove over.
As Scunthorpe retaliated, midfielder Matthew Sparrow fired in a left-foot shot just over the top.
The home side began to dictate a little more and John Ruddy was called into action to stop a header from Richard Hinds and then Ian Baraclough cracked in a low shot which skidded wide.
Lax defending by Scunthorpe allowed the visitors to come back strongly and keeper Paul Musselwhite pulled of a fine double save, first from Ciaran Toner and as the ball fell away the lively Chillingworth cracked the ball in and the keeper touched the ball over the bar.
Chillingworth then got free again to cut in and from 18 yards he was well off target.
Against the run of play Scunthorpe took a 34th minute lead. Sparrow whipped in a shot which was blocked and Richard Kell followed up to squeeze the ball under Ruddy.
Scunthorpe upped the tempo after the break and the visitors only managed one effort on goal and that came after they were two goals down.
The lively Chillingworth got in a strong header which Musselwhite saved under the bar.
But at that stage the writing was on the wall as skipper Crosby had got in a deft 63rd minute flick to establish a solid lead.
Steve Torpey almost added another with a ball that Ruddy flicked on to the bar, but Taylor's appearance brought more pace and he made it three with a superb low shot from 20 yards in the 81st minute, and two minutes later he reached a Peter Beagrie cross to complete the rout.