The Cumbrians led through Sean O'Hanlon's header midway through the first half and made sure of a first win in seven games with a second-half strike by teenager Mark Beck, his sixth goal of the season.
Brentford had a definite edge in first-half possession, but failed to make the most of the chances they created and it was Carlisle who snatched the lead in the 22nd minute when Jon-Paul McGovern's free-kick was met by O'Hanlon, who beat goalkeeper Simon Moore with a looping header from 12 yards.
Carlisle almost added to their advantage soon after when Moore had to make a smart double save, initially to block Beck's header and then to get down at the feet of Matty Robson, who had followed up.
Carlisle goalkeeper Mark Gillespie proved equally alert at the other end, diving full-length to divert Adam Forshaw's 25-yard drive for a corner.
Bees went close again when central defender Liam Moore blasted a rasping right-footed shot over the crossbar from a dangerous position inside the area.
Bees' leading goalscorer Clayton Donaldson should have done better with a free header at the far post, but Carlisle caught the visitors napping in the 54th minute when Brad Potts stole possession and ran through the middle before feeding Beck, who converted from 12 yards.
Carlisle's defence held strong in the face of late Brentford pressure and James Berrett nearly capped a breakaway with a third near the end when Moore only just managed to keep out a piledriver.