The visitors struggled to cope against United's twin strikeforce of target man Steve Torpey and leading marksman Billy Sharp.
Only a great save by goalkeeper Mark Goodlad denied Sharp a goal in only the second minute.
But Sharp did pounce with the opening goal eight minutes later when he applied the finishing touch from close range after Steve Foster's header from a corner had been turned against the underside of the bar by Goodlad.
As Port Vale tried to get themselves back into the game striker Akpo Sodje missed a good chance when he fired over from close range.
New signing Richie Humphreys also went close with a cracking left-foot volley that brought the best out of Scunthorpe keeper Joe Murphy.
At the opposite end Sharp broke free of a square Vale defence only to be denied by a great double save by Goodlad.
But Sharp struck again on the stroke of half-time with a brilliant far post volley after an inswinging corner from Ian Morris had been flicked on at the near post.
That left the visitors with the proverbial mountain to climb in the second half.
They thought they had reduced the arrears in the 54th minute when Sodje netted from close range only to be denied by a linesman's flag for offside.
But Scunthorpe made sure of that first home win when Morris made it 3-0 in the 65th minute with a deflected shot from the edge of the box that found the bottom corner.
Winger Cleveland Taylor might have added to the score when twice he broke through a fragile Vale defence but each time failed to find the finishing touch.
The visitors used all three substitutes to try and get themselves back into the game but leading marksman Leon Constantine had little support in front of goal.
It was a miserable night for Vale who slipped to only their third defeat of the season.