United were looking for back-to-back victories as they went to Glanford Park for their second league away game of the new season.
But it turned into a disappointing afternoon as they missed chances to put the points to bed only to be undone by a crunching drive from Jordan Hallam just past the half hour.
Manager Chris Beech was without Omari Patrick and Gime Toure, who had both picked up knocks, so that meant a return to the starting fold for Lewis Alessandra and a first start for the club following his loan move from Preston for Ethan Walker.
It was nip and tuck through the early exchanges with Carlisle enjoying a large amount of the possession. But the first moment of real pressure came when Hippolyte took charge of a 24-yard free kick.
It was bent towards the back post, but Mellish was there to shepherd it away. A poor corner was recovered quickly and Farman had to jump high to claim it before Loft could connect with his head.
The Iron sparked a scramble on 13 minutes when a long throw pinged around inside the box. It eventually came to Spence, on the edge of the area, but he was quickly closed down by McDonald and the shot whistled over the bar via the defender's thigh.
Carlisle thought they'd taken the lead on 17 minutes when Mellish executed a strong tackle tight by the right hand touchline. It was fed quickly inside to Kayode and it opened up for him as a defender lost his footing. The big forward kept his composure and awareness as he slid it across to the unmarked Ethan Walker, who was advancing on the penalty spot. The away side were set to celebrate until Watson somehow pulled off an unbelievable one-handed save.
The Scunthorpe response was a break through the middle which brought Gilliead into an advanced position. He went for broke from distance and his shot bent harmlessly away.
Another good visiting move came when Alessandra pulled wide to take a pass from McDonald. He brought Guy into play, and Kayode gambled on a near post cross. He got there but his touch was too close to Watson.
A long throw from Alessandra followed and the slightest of clips from Kayode caused real confusion. Walker was deep, and his first cushioned touch set up the volley, but Watson was there sharply once again to make a save.
It was all about Carlisle and a free kick from Tanner brought half sights of the nets for Hayden and Kayode. There was a shout for handball as a deflection struck Cordner, but the referee was quick to show he had no interest.
For all of their domination the orange shirts were almost undone when O'Malley went on the overlap. He fizzed an inch perfect cross across the face of goal but Loft somehow sent his close range touch the wrong side of the post as he came under strong and good pressure from McDonald.
It was a short-lived reprieve as Mellish misplaced a pass in midfield. Gilliead fed it on to Jordan Hallam and he thundered a low drive into the bottom corner, leaving Farman with no chance.
Striker Ryan Loft looked to extend the lead just before the break when he charged down a clearance from Hayden. He went for a curled effort from the angle of the box but it was always heading wide.
A dipping corner from Guy in time added on for the half was won by Hayden, and all Watson could do was beat it away as it threatened to cross the line. Carlisle shirts were lined up but the referee alleviated the pressure as he blew his whistle.
The second half started in much the same way as the first, with both sides probing and looking to cross, but it stayed tight with defences on top.
A bender from Gilliead had to be watched by Tanner though, as it bent deep. He put it behind and Bedeau was disappointed with his header from the resulting corner as he nodded it to towards the corner flag.
It was another fantastic save from Watson which denied Mellish an equaliser when he guided a great cross from Walker at the top corner. The stopper threw himself high and spectacularly clawed the goal bound headed effort away from the nets.
The Cumbrians almost picked the lock when a flighted pass from Furman found Walker on the sprint. He volleyed it over Watson and he was disappointed to see it loop onto the roof of the net.
Farman had to be off his line smartly at the other end to intercept a through ball from Loft, as Spence bore down, and the keeper was in action moments later when he stooped to stop Spence from making a delivery.
Carlisle maintained the tempo and more good work between Alessandra and Walker saw the latter go past his man with a deft touch off his toe. Watson was well placed to gather it in as it came from wide when it skipped up from the surface.
There was more chaos in the Iron area when a Guy corner was kept alive, but a clear route couldn't be found and the back line stayed strong.
A winding run from Kayode brought another corner as his attempt spun off a boot and wide of the mark.
Teenager Ethan Walker thought he'd done the trick with 10 minutes left to play when he dropped a shoulder to leave his man in his wake. He pulled the trigger and the Carlisle contingent were left with their heads in their hands as it crept a whisker wide of the upright.
Hallam spurned a late chance to seal the points when he blazed over, having been sent through by another slide rule pass, and Alessandra was denied at the other end when he stayed on his own at the far post.
A header from Hayden was going in but Watson stayed big to beat it away. The vice-captain drilled a late shot from distance into the stands as the Cumbrians continued to push, but Farman had work to do as he tipped a 24-yard free kick over the bar in time added on.
United looked to get the ball back, but the Iron held out to take the three points.
Scunthorpe United - Hallam (36)
Scunthorpe United - Spence (73), Beestin (85)
Scunthorpe United - Watson, Bedeau, Gilliead (c), Loft, Hippolyte, Hallam, Spence, Vincent (Beestin 78), Cordner, Hornshaw (Butroid 88), O'Malley (Onariase 75). Subs - Kelsey (gk), Eisa, Green, Jarvis.
Carlisle United - Farman, Tanner (Hunt 85), Hayden, McDonald, Anderton (c), Furman (Reilly 71), Guy (Devine 77), Mellish, Walker, Kayode, Alessandra. Subs - Dewhurst (gk), Riley, Charters, Bell.
Referee - Peter Wright
Assistant Referee 1 - David Hunt
Assistant Referee 2 - Joe Simpson
Fourth Official - Anthony Moore
Attendance - behind closed doors