Carlisle missed a series of first-half chances as they slipped to Scunthorpe made it four wins on the bounce.
Substitutes Matt Sparrow and Martyn Woolford combined to put Scunthorpe in front, Sparrow heading in Woolford's left-wing cross on 61 minutes.
Scunthorpe struck again in the 73rd minute when striker Paul Hayes provided the finishing touch after a long-range effort from Woolford.
Carlisle's Danny Carlton pulled a goal back when he scrambled the ball in.
Scunthorpe: Murphy, Byrne, Mirfin (Iriekpen 46), Pearce, Williams, Thompson (Sparrow 59), McCann, Togwell, Hurst (Woolford 58), Hayes, Hooper.Subs Not Used: Lillis, Morris.
Goals: Sparrow 62, Hayes 73.
Carlisle: Williams, Raven, Livesey, Murphy, Horwood, Taylor, Bridge-Wilkinson, Thirlwell, Hackney, Graham (Dobie 71), Carlton.Subs Not Used: Howarth, Joyce, Keogh, Madine.
Goals: Carlton 77.
Att: 5,188
Ref: Mike Thorpe (Suffolk).
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