The deserved win never looked like it was going to materialise as visiting goalkeeper Jon Brain put in an outstanding performance which threatened to frustrate the home side.
The first half proved to be a dull affair which only burst into life when Brentford finally built up some pressure in the last five minutes.
Brain was called into his first meaningful save when Nathan Elder saw his header terrifically pushed onto the inside of the post by the keeper.
This gave the home side the push they needed as they suddenly attacked at will.
First Ricky Shakes saw his goalbound shot brilliantly blocked by Macclesfield defender Ryan Cresswell, before Alan Connell saw Brain deny him with a point-blank save from six yards out.
The Bees began the second half on the front foot with another blocked goalbound shot, this time from Gary Smith, being well defended.
Continuing to dominate, Poole then tried his luck with a 20-yard free-kick which Brian gathered at the second attempt.
At the other end, Jamie Tolley threatened with a flicked header from Neil Ashton's long throw-in though it never caused any real danger for Simon Brown in the home goal.
However, it was Brentford who continued to threaten. Elder was once more denied by inspired goalkeeping from Brian, who turned the striker's effort onto the underside of the bar before he then kept out Connell's fiercely struck volley.
However just as it looked as if Macclesfield would come away with a point, deep into stoppage time Connell played the ball to the far post where Poole was able to head home a deserved winner.