Both sides had their injury problems early on as United striker Danny Carlton pulled up in the pre-match warm-up and was replaced in the starting line-up by Danny Graham. Then Tranmere lost livewire winger Chris Shuker after just nine minutes with Jennison Myrie-Williams taking over.
Tranmere could not capitalise on early chances but went ahead in the 16th minute. Paul McLaren netted his second of the season with an shot from the corner of the box after linking-up with Myrie-Williams from a short corner. McLaren's effort flying into the net with the aid of a deflection from Carlisle defender David Raven.
Joe Garner had no luck with two efforts for Carlisle and Tranmere were unlucky not to get a second goal in the 39th minute. A Chris Greenace shot struck the inside of a post and the ball appeared to be over the line before it was hooked clear.
But the Merseysiders did get a second before the break with Antony Kay volleying home in superb style from a partially cleared corner in the 45th minute. Carlisle could not capitalise from a good opening to the second half when Danny Livesey was unlucky to see a header cleared off the line by McLaren.
The visitors thereafter rarely looked like saving the game. Calvin Zola saw a 57th minute shot for Tranmere turned over by keeper Keiren Westwood and, at the other end, a header from Marc Bridge-Wilkinson, who picked up his fifth booking of the season during the match, went across the face of the goal.
Carlisle finished strongly but substitute Kevin Gall hit the underside of the bar from close range and then Joe Garner headed wide. McLaren took star billing for the winners, but it was a fine all-round team performance which won the day as United disappointed their large travelling contingent.