Midfield man Grant McCann rifled a first minute effort just over, before striker Paul Hayes then tested keeper Danny Coyne with an angled drive.
Boro gradually began to get to grips with the game with Gary O'Neil a major influence in the middle of the park.
The pace of striker Leroy Lita was also a big threat to the home defence and he might have opened the scoring after wriggling free into the box past defender Rob Jones, only to be denied by a good save from keeper Joe Murphy.
Boro finally went ahead in the 28th minute with a brilliant move. O'Neil flighted an inch-perfect pass to the edge of the box where winger Adam Johnson popped up to lift a first time shot past Murphy with an excellent finish.
It was a goal which would have graced the Premier League last season and it's quality like this that make Boro favourites to go straight back up.
But Scunthorpe almost bounced back four minutes from the interval when McCann thundered in a left foot shot that dipped just inches over.
There was heartbreak for United at the start of the second half when referee Michael Oliver twice pointed to the spot against them.
The first was in the 48th minute after Michael O'Connor chased back into the box to tackle Boro's Rhys Williams.
Johnson took the penalty but saw it half-blocked by Murphy, only for the referee Oliver to point to the spot again as the United keeper tried to stop a follow-up effort from the Boro winger.
Johnson kept his nerve to crack the second penalty past Murphy and give his side a more comfortable 2-0 lead.
But Scunthorpe continued to battle and were unlucky not to reduce the arrears in he 58th minute when a header from Jones was cleared off the line by David Wheater.