The Cumbrians were left to rue a series of missed chances in a first half in which they dominated.
Leading marksman Danny Graham set the tone when he fluffed a simple close-range opportunity in the early stages.
Then it was Scunthorpe keeper Joe Murphy who frustrated the visitors with three good saves to deny first Danny Carlton, then Simon Hackney and finally Cleveland Taylor.
But a mistake by Murphy gave Taylor an opportunity he should have done better with against his old club when he fired into the side-netting.
It was a double substitution in the 58th minute that turned the game in Scunthorpe's favour when they brought on wingers Matt Sparrow and Martyn Woolford.
Three minutes later the two combined to put Scunthorpe in front when Woolford's good cross from the left was flicked on at the near post by Paul Hayes for Sparrow to score at the far post with a forceful header.
The home side went close again in the 71st minute when striker Gary Hooper flicked a shot past keeper Ben Williams, only to see it scrambled off the line by centre-back Danny Livesey.
Two minutes later though Scunthorpe did make it 2-0 when the impressive Woolford's long-range shot was only half-stopped by Williams and Hayes followed up to force the ball home.
Carlisle reduced the arrears in the 77th minute when Carlton scrambled the ball home from close range from a right-wing cross by Taylor.
The visitors then squandered a couple more good opportunities to rescue a point when both Taylor and Hackney should have done better with openings that came their way.