United boss Steven Pressley went with a back three, complemented by wing backs, as Gary Liddle and Peter Grant stepped back into the starting line up for the away trip to in-form Tranmere.
Captain Danny Grainger missed out with a hamstring injury and Hallam Hope dropped down to the bench as the Cumbrians came up against the division's in-form outfit.
United were on the attack early when they edged their way down the left flank with O'Hare and Devitt working space between the right-sided defenders. Stand-in left wing back Tom Parkes called for it as he came forward and his cross bent towards the penalty spot. Ellis jumped high and he did well to nod it clear.
Carlisle came again when Devitt was given time in midfield. He turned and picked out O'Hare who immediately got his head down to go on a run. He went for a shot as he reached the edge of the box but it was straight at Davies.
A cross from Ridehalgh had Collin scrambling as he looked to get his side going at the other end, but Grant was back to cover and he helped to shepherd it away. The Whites attacked again with a cross from the right from Caprice which found Norwood in a good area. He dived to meet it but his header bounced just wide of the upright.
Carlisle responded well and a flowing move down the left saw Parkes overlap as O'Hare and Devitt combined to work space. He took a touch and shot across the face of goal but Davies was able to breathe a sigh of relief as it sped past the post.
And Thomas produced an almost carbon copy effort moments later when he ghosted forward and called for the ball. Devitt fed it to him, but he couldn't quite get the angle he needed and he swept it wide.
United keeper Adam Collin was comfortable when Norwood tried his luck with a 28-yard free kick, but he had to be on his game when Banks dropped his shoulder and put his laces through a crisp volley from a similar distance. The keeper saw it late but he got down smartly to palm it away.
It was the visitors who should have taken the lead on the half hour when Slater flighted a beauty of a pass into the channel. Thomas got there first, and he left Ellis for dead as he spun with the ball at his feet. A rolled pass brought a firm toe poke from O'Hare, from just 10 yards out, and he was disappointed to see it crash back to safety off the underside of the bar with the keeper well beaten.
Devitt was next to test the target when he held his ground to see the outcome of a midfield tussle between Miller and McCullough. The United man won it, and Devitt wasted no time in setting himself for the shot. Davies dived as it swirled in the air and he was pleased to be able to beat it away with his fists.
A volley from Jennings didn't seem to cause Collin too many problems as Tranmere were restricted to shooting from distance, but the Cumbrians were left to rue the fact that they hadn't converted good football into goals with the last attack of the first half when the hosts made the most of a half cleared corner. Ellis and Perkins combined to make space for a cross and Ollie Banks said thank you very much as he was able to finish off a crunching delivery from very close range.
Trickery from Callum O'Hare earned his side a free kick on the angle of the box at the start of the second period but Devitt wheeled away in frustration as his direct shot fell onto the roof of the net.
Collin had to keep his eye on a volley from Perkins as the game started to open up, and he collected it well as he moved to get his whole body behind the shot. The Cumbrians also had to deal with a well-crafted move which saw Perkins eventually release Banks on the right wing. His low, rasping drive was blocked by Gerrard just in the nick of time as Norwood steamed in.
But Tranmere doubled their advantage for the afternoon on 64 minutes when they somehow managed to bundle their way down the right wing, with Banks heavily involved. It was his cross which scythed through the United back line and the predatory James Norwood took his personal tally to 29 for the campaign as he stayed alert to bundle the ball over the line at the second attempt, with Collin having made an initial superb point-blank save.
The Whites were suddenly full of confidence and shots from Norwood and Banks went close, with Carlisle wasteful with set pieces at the other end, and the game settled into a battle for possession in midfield as the hosts kept things tight.
Collin made a fine save from Harris when he instinctively shot late in the day, but an unguarded run from defender Manny Monthe from the resulting corner left him with the simple task of guiding his header into the roof of the net as a three-goal match-winning cushion was formed.
Callum O'Hare sent a free kick from wide just past the post in time added on, but it was a disappointed Carlisle contingent who left the stadium having allowed the upper hand to slip in a game that had showed much first half promise.
Tranmere Rovers - Banks (45), Norwood (64), Monthe (83)
Tranmere Rovers - Davies, Ridehalgh, Monthe, Norwood, Jennings, McCullough (Harris 10), Caprice, Ellis, Perkins, Morris (Gilmour 76), Banks (Smith 85). Subs - Pilling, Buxton, Mullin, Dagnall.
Carlisle United - Collin, Miller (Hope 59), Liddle, Gerrard, Grant, Parkes, Slater, Jones, O'Hare, Thomas, Devitt (Etuhu 72). Subs - Gray, Kennedy, Simpson, Scougall, Branthwaite.
Referee - Mr Scott Duncan
Attendance - 8,095 (910 away fans)