Kevin Blackwell's men, now four games without a win, can have few complaints after playing second fiddle for long spells to the Iron.
There was little to choose between the two sides in the early stages, with Sheffield failing to make the most of the possession they enjoyed.
It was McCann who broke the deadlock in the 22nd minute with a brilliant effort from 25 yards that dipped over goalkeeper Mark Bunn and into the top corner of the net.
That boosted the confidence of a Scunthorpe side also looking for their first win in four games.
They could have made it 2-0 on the half-hour when an excellent move opened up the defence to send full-back Marcus Williams racing free into the box, but he lost his composure and blazed his shot high over the top.
Sheffield stirred just before the interval and striker Ched Evans might have done better when he headed wide at the near post from a cross by Andrew Davies.
Veteran winger Glen Little also went close with a 25-yard effort that dipped just over the bar.
Sheffield were back on level terms after 52 minutes when Evans applied the finishing touch from close range.
But three minutes later, Scunthorpe were back in front from a quickly taken throw in which saw striker Gary Hooper lay the ball off into the path of Paul Hayes, who rifled an angled drive past Bunn in the far corner of the net.
Inspired Scunthorpe then made it 3-1 in the 59th minute with another terrific move that sliced open the Blades defence.
When a shot from midfielder Josh Wright came back off the inside of a post, it was McCann who reacted quickest to steer his shot into the back of the net for this second goal of the game.
In the closing stages the Blades looked a well beaten side, unable to apply much pressure on Joe Murphy in the Scunthorpe goal.
In stoppage time it was the home side who nearly struck again when a cross from substitute Jonathan Forte found Martyn Woolford whose header was held underneath the bar by Bunn.
Defeat leaves Sheffield struggling to keep pace with the early leaders at the top end of the table, while victory puts some real daylight between Scunthorpe and the bottom three.