Josh Wright had put the Iron ahead after 19 minutes, but the lead lasted just five minutes. The visitors then scored four more times - all of which Ian Baracough, the Iron caretaker manager, will feel could have been avoided - before Martyn Woolford got a late consolation that was the least the Iron deserved.
The Iron were backed by a crowd of 9,077, a record for Glanford Park. They took just 21 seconds to get a shot on target when Jonathan Forte made a nuisance of himself in the box, with Woolford bringing a save out of Tomasz Kuszczak.
Scunthorpe created several opportunities inside the opening 10 minutes.
Michael O'Connor hit a low shot from distance that was straight at Kuszczak, with Wright rasping a drive just wide and Eddie Nolan firing a low shot at the keeper.
The visitors looked dangerous on the counter-attack, with Javier Hernandez caught offside after 14 minutes when he broke through on goal.
The Iron took a deserved lead after 19 minutes. Woolford ran past Wes Brown and Darron Gibson, before laying the ball off to Wright.
Wright, a couple of yards outside the area, took one touch before firing the ball into the top left corner with an excellent shot.
The lead, however, did not last long. There were 22 minutes on the clock when Gibson allowed Chris Smalling's long-ball to bounce once on the edge of the area before lobbing it into the far corner of Joe Murphy's net.
That goal was a reality check for the Iron. For all the domination they had enjoyed until then, the visitors only needed one opportunity to score.
Chances continued to come for the Iron, with Cliff Byrne heading over from a corner after 31 minutes.
The visitors created their second chance of the match after 36 minutes, and went 2-1 ahead. Smalling turned the ball home from Ji-Sung Park's cross.
Kuszczak had looked uncomfortable at dealing with shots from distance, and almost gifted an equalising goal to Forte when he misjudged a shot from the Iron forward, the ball palmed off his gloves but spun across the full length of the goal and allowed the Polish keeper time to reclaim it.
The match was won by Manchester United early in the second-half, even though Scunthorpe again created the first opportunity when Byrne's header from a deep Nolan cross was headed against Rafael.
Their third chance came three minutes after the restart, with Michael Owen putting them 3-1 ahead. He was played in by Federico Machedo to finish of a quick counter-attack, although the common suggestion is he has lost his pace he was never going to be caught by David Mirfin or Niall Canavan.
Park smashed home the fourth with a low shot after 53 minutes when the Iron failed to clear a corner.
The home players lost a bit of belief and were limited to long shots from Woolford and O'Connor.
The score was 5-1 when Owen was on hand to tap the ball home when Park's shot was saved by Murphy.
The introductions of Bobby Grant and Matt Godden - making his competitive debut - helped the Iron continue to create chances.
Their best chance of scoring still looked like it would come via a fumble from Kuszczak, who was lucky to see a free-kick from Grant go over the crossbar after he struggled with the movement of the ball again.
He had to be alert to turn another shot from Grant over, but was beaten in stoppage-time when Woolford forced the ball home from Wright's cross. He was aided by a deflection off Gibson, but the goal was deserved.