The Bees came into the game in second spot but forced only one save from Macc keeper Jon Brain all afternoon.
Macclesfield, however, created a string of chances producing a scoreline that was hardly flattering.
The first chance came in the 11th minute when 20-year-old striker Gareth Evans forced a sharp reaction save from Ben Hamer with a powerful 20-yard drive.
Evans beat Hamer in the 13th minute after a clearance had been charged down by Emile Sinclair only for the strike to be ruled out for offside.
Centre-back Richard Walker was next to go close when he saw his six-yard header blocked on the line by the alert keeper.
Hamer had to be at his best again in the 42nd minute when Macc winger Danny Thomas produced a powerful volley that had the gloveman scurrying across his goal.
However, Hamer was left stranded in first-half stoppage time when he came for a bouncing ball outside his area, and the pacy Sinclair, on loan from Nottingham Forest nodded the ball past him before planting a shot into the empty net for his first goal.
Sinclair might have had a second on 47 minutes only for Hamer to produce a sharp diving save.
Macclesfield virtually sealed the game on 58 minutes when right wing-back Izak Reid was brought down by Ryan Dickson for Evans to thump home his seventh goal of the season from the spot.
Macclesfield might have had another on 66 minutes when Jamie Tolley muscled his way to the byline but his low cross was taken off the foot of Gareth Evans by a late lunge from Hamer.
All that Brentford could muster was a tame header from Mark Phllips that gave Brain an easy save in the 68th minute.