Carlisle came to Whaddon Road fresh from a 6-0 win over Stockport last week while Cheltenham fell to a home defeat against Mansfield.
However, the form book was turned on its head as Cheltenham produced a tenacious performance and a goal from Northern Ireland international Grant McCann that was enough to win the game.
McCann had been an injury doubt right until the eve of the game but he was back to his incessant best and collected the man-of-the-match award.
His goal arrived after 64 minutes when defender Gavin Caines crossed from wide on the right. Striker Kayode Odejayi headed it down, midfielder Brian Wilson laid a pass to McCann and he crashed a shot with his right foot past goalkeeper Keiren Westwood from 10 yards.
The goal was one of the few bright moments of a second half that failed to match the promise of the first.
Within five minutes of the start both sides had gone close to scoring with Cheltenham goalkeeper Shane Higgs saving well from Derek Holmes and Jamie Victory seeing a header cleared off the line by Danny Livesey.
Higgs then saved well from Simon Hackney and the same player saw a shot booted clear by Caines as the visitors looked the more likely to score in the opening stages.
Cheltenham's Wilson went close with a couple of efforts in the moments leading up to half-time, curling one shot wide and grazing a post with another one, but it was generally a game between two well-matched sides.
After the goal, Carlisle, who have risen to sixth in the League Two table, applied heavy pressure to the Cheltenham goal but to no avail.
Holmes flashed a shot over the bar and striker Karl Hawley had the ball in the net deep into injury time only for the goal to be disallowed for offside.