Craig Curran scored Tranmere's winner as they ended Carlisle's unbeaten record in League One. Danny Graham missed a great chance to put the Cumbrians in front when he rounded Rovers keeper Danny Coyne but saw Ian Goodison clear his shot.
Carlisle keeper Keiren Westwood denied Calvin Zola and Robbie Stockdale with a superb double save.
But Paul Arnison's slip before half-time let in Chris Shuker, who teed up Curran to blast home from six yards.
Carlisle: Westwood, Arnison, Livesey, Raven, Aranalde, Gall (Carlton 73), Thirlwell, Bridge-Wilkinson (Lumsdon 73), Smith (Hackney 64), Garner, Graham.
Subs Not Used: Howarth, Worley.
Booked: Garner, Livesey.
Tranmere: Coyne, Stockdale (Kay 85), Goodison, Chorley, Sherriff, Shuker, McLaren, Jennings, Davies, Zola (Curran 17), Greenacre, Curran (Tremarco 79).
Subs Not Used: Achterberg, Jones.
Goals: Curran 42.
Att: 6,556
Ref: Eddie Ilderton (Tyne & Wear).
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