It was their third home win in a week and lifted them five points clear of the relegation zone.
After being presented with an anniversary plaque from Football League chairman Greg Clarke, Scunthorpe raced into an early 2-0 lead.
Striker Akpo Sodje headed them in front from a left-wing cross by Mark Duffy after 17 minutes - his third goal in the last three home games.
Three minutes later skipper Paul Reid powered home a header from a right-wing corner by Duffy.
It threatened to be a tough night for Carlisle, who arrived at Glanford Park unbeaten in their previous four games. But they were thrown a lifeline in the 45th minute when midfielder James Berrett tried his luck from long range and saw his shot squirm into the net under 'keeper Sam Slocombe.
Scunthorpe nearly struck back immediately in first-half stoppage time when a header from Sodje came back into play off the far post.
There were chances at both ends in a frantic second half, Jimmy Ryan and Karl Hawley both within a whisker of a third goal for Scunthorpe, while only two excellent saves from home keeper Slocombe denied the Cumbrians an equaliser.
Finally it was Sodje who settled things when he raced clear in stoppage time for Scunthorpe to make it 3-1 with his second goal of the game.