With both teams hopelessly out of form - Carlisle had lost their last three league games - a goalless draw seemed likely until the Bees' hapless defence shipped two goals midway through the second half.
Neale McDermott was the star for Carlisle, setting up the first goal before bundling in the second to halt the Cumbrians' recent slide.
McDermott's 69th minute pinpoint corner was pounced upon by the soaring Derek Holmes, who met it with the merest of glances to finish past the stranded Clark Masters.
Just five minutes later Kevin Gall's lightning break saw him run from his own half and past two defenders before crossing for the incoming McDermott to knock the ball in with his knee from close range.
The scoreline was tough on Brentford who had the best chances throughout the game.
Simon Cox should have had a goal allowed when his free-kick drifted into the net without anyone getting a touch, but it was bizarrely ruled out for offside.
Earlier Charlie Ide missed an open goal after Carlisle captain Kevin Gray made a poor pass back to his keeper Keiren Westwood.
Ide jumped on the mistake and rounded Westwood, but with the goal gaping, he scuffed his shot and Gray made up for his error with a timely clearance.
Bees strikers Calum Willock and Jo Kuffour were a constant threat and both went agonisingly close with long-range looping volleys that had Westwood at full stretch.
Ide went close again but after Carlisle's opening goal there was only ever going to be one winner.
Gall almost added a third late on when his mis-hit cross looked to be heading in before Masters clawed it away from under his crossbar.
And Westwood compounded Brentford's misery with an amazing stopping time save from Willock to send the Londoners back home without so much as a consolation.