United were in Cleethorpes for the second time in the space of a month for their rearranged League Two fixture, with the first attempt having fallen foul of some heavy rain and a 34th minute abandonment.
And the away team starters were unchanged from the weekend trip to Newport, where a late goal from Corey Whelan had earned a draw.
Sonny Hilton didn't travel, as he suffered from a rolled ankle picked up at Rodney Parade, and that meant that second-year Ryan Carr was handed another call-up to the bench.
Callum Guy made his 100th appearance for the club, having notched his first goal in a blue shirt three games ago, with Whelan once again handed the captain's armband.
There were a few raised eyebrows as rain started to fall heavily half an hour before kick off but that was quickly followed by relief when it abated, taking away the threat of another waterlogged pitch.
United got themselves into a good position with just two minutes on the clock when Guy looked up in midfield. A rifled through ball set Stretton on a run, and he used pace to get into the area. His low cross was aimed at Dennis but Crocombe dived to cut it out.
The Mariners had a good spell of pressure with crosses from Efete on the right providing a test. Amos recycled a deep one and his delivery eventually came to Hunt. A drilled effort was picked up by Holy at the second attempt.
Carlisle countered with some neat touches and Stretton was once again in a good area out on the left flank. He droped a shoulder and stepped inside, and he calmly rolled it for Moxon to hit. The midfielder became the latest player to register his first goal for the club with a thunderbolt of a 23-yard thump.
It was the away side who were dangerous again when Dennis controlled with his chest with his back to goal. Armer was in space, but his cross-shot from an angle struck Waterfall, who had scampered to cover.
A wicked ricochet from a charged down Huntington clearance had Taylor interested for the home team as it skipped and spun its way into the area. Mellish was fouled as he won the race to get to the loose pieces.
A quieter period followed and Hunt tried to take matters into his own hands when he robbed the ball off Guy. His swiped connection from distance was always going wide.
United went on the break after Mellish had slid in to stop a shot, with the crowd screaming for a free kick. The visitors ignored that, and Stretton was sent on a sprint. He used pace to cover the distance, leaving the chasers in his wake, but Crocombe dived to make a two-handed save when the clipped shot came.
Grimsby were close on 29 minutes when Khan ghosted his way through a packed midfield. It was suddenly there to go for and he kept it low on the run as he aimed for the bottom corner. Holy was beaten, but it was always heading towards the backing boards.
Manager Paul Simpson switched to a back four, with Mellish pushed into midfield, as he looked to stifle the threat of a build in home momentum, and it was a tactic that worked, with the Holy nets largely protected.
And it was an overload from the red shirts that nearly paid dividend as Dennis and Gibson used Moxon to edge their way forward. Armer came late in support, and Crocombe had to stretch to fingertip it away from the lurking Kris Dennis.
The corner from Moxon went low to the front stick, and a touch on the lean from Huntington left the defence flat-footed. Mellish tried to control and shoot but he was judged to have handled as it came his way.
Khan sent one over from distance at the other end when he sprinted into space, and the same player popped a 28-yard free kick over the wall, but into the safe hands of the big United stopper with Grimsby struggling to make any real impact.
The lead was doubled on the stroke of half-time when Efete lost his bearings as he tried to get a pass back to Crocombe. Kris Dennis was on his toes and he netted his eighth of the season (his tenth for the club in total) as he touched the gift past the keeper before stroking it over the line.
Carlisle worked hard to keep things tight after the break, and it wasn't until the 55th minute that the Mariners had half a sight. Khan spun his marker and volleyed, but it sailed over the bar.
A corner on 58 minutes was nodded wide by Waterfall, with the visitors settled in their shape, but substitute Lewis Richardson injected some belief when he wormed his way into the box. The ball was put behind, and Moxon twice defended as the corner and the follow up came at his chest.
Grimsby threw more men forward, but a poor set piece delivery let some of the pressure out of the valve. But the hosts were right back in it when an initial clearance from a dipping corner left Khan with time. He wasn't closed down, and Michee Efete was able to make amends for his error as he bundled the ball over the line when it rumbled onto his boot.
The lively Richardson forged a run to the edge of the box moments later and he was tripped by Guy on the line of the 'D'. Khan took it on, but it was stopped the wall. A second foul by Armer, this time on the byline, gave Khan the chance to loft it in but Huntington leaped to nod it to safety.
Carlisle looked edgy and they caused their own problems with two rushed passes in midfield. Richardson took it on, but his cruncher struck a thigh and swirled behind.
United heads calmed, and a foul on Dennis gave Moxon the chance to swing it in from deep. Huntington got there, but his header was too close to Crocombe.
Intelligent game management came into play as the home team found themselves at arm's length, but Huntington was needed to clear at the near post deep into time added on when Richardson tried to squeeze it in from a tight angle.
Harris needed treatment when he was clattered inside the box as another ball was sent in there, and it was the 144 away contingent who celebrated as they watched their team see their first away win of the season to a successful conclusion.
Grimsby Town - Efete (65)
Carlisle United - Moxon (7), Dennis (44)
Grimsby Town - Simmonds (72)
Carlisle United - Guy (67), Armer (69)
Grimsby Town - Crocombe, Maher, Amos (Kiernan 84), Waterfall (c), Efete, Maguire-Drew, Clifton, Khan, Taylor (Orsi 60), Hunt, Simmonds (Richardson 60). Subs - Glennon, Smith, Green, Holohan.
Carlisle United - Holy, Whelan (c), Huntington, Mellish (Charters 79), Back, Gibson (Harris 70), Guy, Moxon, Armer, Stretton, Dennis. Subs - Kelly (gk), Ellis, Bollado, Carr, Idehen.
Referee - Simon Mather
Assistant Referee 1 - Michael George
Assistant Referee 2 - Declan Ford
Fourth Official - James Westgate
Observer - Mark Brown
Senior Observer - Clive Oliver
Attendance - 6,447 (144)