Charlie MacDonald got the only goal of the afternoon when he volleyed home a Sam Wood cross in the 15th minute and then watched his team-mates miss a host of chances which almost cost them dear.
Nathan Elder shot against the post from ten yards after being put through by Josh Wright and Marvin Williams shot straight at Jonny Brain in the Macclesfield goal after an incisive MacDonald pass.
Adam Newton missed an even better opportunity when he slipped in front of goal with only Brain to beat and the visitors almost made Brentford pay.
Shaun Brisley could have snatched a point when he shot over from ten yards after Brentford had failed to clear a corner and Ben Hamer in the home goal had to dive full-length to turn away a Terry Dunfield drive.
But a point would have been much more than the visitors deserved.
Brentford carved them open at will after the break and should have sealed the game by the hour mark.
Brain produced a brilliant full-length save from Marcus Bean's long-range effort and Glenn Poole sliced a shot wide.
Newton also shot narrowly wide from distance and John Halls headed over as the home side dominated.
Simon Yeo had been wasteful in front of goal for the visitors in the first half, shooting weakly at Hamer from ten yards and also into the side-netting early on.
The dangerous Danny Thomas also failed to test Hamer from a good position in a disappointing first half.