Just one defeat in nine games had seen United open up a 17-point gap to bottom spot and they were back at Brunton Park to face Colchester as they looked to keep their impressive run going.
There was just one change to last week's starting eleven with Max Hunt stepping up to cover for the suspended Byron Webster.
Striker Josh Kayode and midfielder Mo Sagaf were drafted onto the bench for what was a very attack-minded approach from head coach Chris Beech.
United kicked towards the Warwick Road End, as the U's won the toss, and good work from Watt saw him carry the ball through midfield. Mellish was set free on the left flank, and his low cross had to be cleared as Patrick checked his run. Watt recovered the clearance, and McKirdy took over with a shot that was blocked at source.
It was a good start from the Blues and a clever run from Alessandra created more space for Mellish to exploit. His cross came to McKirdy, and a corner was won as he went for goal. The delivery from Watt was deep, and Hunt did well to nod it back into the mix. It eventually dropped in front of Anderton and his 19-yard volley wasn't too far away.
Colchester responded with a cross from Poku which was heading straight to Harriott, who was up in support of the front line. Norris took it with his toe, preventing the shot from his strike partner, and the low punt which followed was easily cleared.
The away side were dangerous when Nouble twisted and turned before having the ball taken off his toe and sent behind for a corner from a sliding challenge. Pell was up for the cross, but it skimmed past his head and Hunt gratefully swiped it away.
Carlisle lifted spirits again on 19 minutes when Watt pinged a fast pass at Mike Jones. He sent Gethin Jones on the overlap, and a cracker of a delivery arrowed across the face of the target, but it was just an inch too far in front of the strike force.
White shirts broke from the goal kick, and Norris had just one thing on his mind as he bent his run towards the box. The shot had power, but Collin was equal to it as he dived long to beat it away.
There was a great chance for the away side midway through the half when Pell robbed possession tight by the right hand touchline. He muscled his way to the byeline, before cutting it back, towards where Norris lurked. He stumbled as he took a touch and his shot was shepherded away as the Cumbrians regrouped.
United worked their way from back to front on the half hour when Collin rolled the ball to Hayden. He strode forward and brought McKirdy into play, and his cushioned pass bobbled onwards for Watt to hit. He caught it well but it took a deflection and Gerken was able to watch it into his hands.
Collin tipped a late-dipping long-range free kick from Bramall over his bar, and Hayden cleared off the line moments later when an inswinging corner from Bramall threatened to creep in at the near post. The follow up corner from the same source brought a flick from Nouble, and he was set to celebrate until the keeper stretched to make a fantastic save.
It was a good spell for the travellers and Collin saved again when Norris sent a piledriver through bodies. Poku stayed on the front foot and he curled an unstoppable shot from the recycled ball into the bottom corner when he found the slightest of gaps with a crunched left-footed effort.
Colchester stayed forward, and Collin had to stop Nouble as he drilled low at the near post. But the hosts were undone by a set piece as a looped corner from Bramall was nodded home from just two yards out by the prolific Luke Norris.
Striker Josh Kayode came on to make his home debut for the start of the second period, at the expense of Elliot Watt, but it was the U's who fashioned the first chance of the half when Bramall ran across the length of the 18-yard line. He let fly on the run but it spun well wide.
Nick Anderton found himself in a very advanced area as he hassled Eastman and he came away with the ball, which brought movement from Patrick. Alessandra had a shot stifled, and Mike Jones made sure Gerken had to work when he tried his luck from distance.
But a tough afternoon got even harder for the Blues just before the hour when an untidy build up brought an equally untidy shot from Kwame Poku. Hayden got his boot in the way almost at the point of contact, and that caused the ball to spin wildly as it cut the grass. Collin could do nothing as it bent slowly into the bottom corner.
Kayode rattled a shot high when he got half a yard in the Colchester half, as he tried to provide a spark, and he had his heart in his mouth at the other end when he stuck a boot out to get in the way of a free kick from Harriott. Collin stayed calm to pull it into his chest.
Nouble was denied by Collin when he went through one-on-one with 20 minutes left to play, and Pell smashed one wide from distance as chances started to dry up for both sides.
Alessandra almost found a way through with a deflected volley that had Gerken scrambling, and a long throw from the striker found Mellish on the march as he arrived late. His header was heading the right way until the keeper jumped across to grasp it.
Chances were at even more of a premium as the clock ticked down, and Colchester were happy sit on their lead as they went on to claim the points.
Colchester United - Poku (40, 49), Norris (43)
Carlisle United - Anderton (49)
Carlisle United - Collin (gk)(c), G Jones, Hunt, Hayden, Anderton, McKirdy, M Jones, Watt (Kayode 46), Mellish, Alessandra, Patrick (Bridge 80). Subs - Dewhurst (gk), Iredale, Charters, Loft, Sagaf.
Colchester United - Gerken (gk), Jackson, Bramall, Prosser (c), Pell, Norris (Robinson 85), Harriott (Senior 82), Eastman, Stevenson, Nouble, Poku (Gambin 87). Subs - Ross (gk), Welch-Hayes, Comley, Clampin.
Referee - Thomas Bramall
Assistant Referee 1 - Billy Smallwood
Assistant Referee 2 - David Avent
Fourth Official - Simon Clayton
Attendance - 3,769 (146 away fans)