The Dons hit the woodwork twice in the first half through Aaron Wilbraham and skipper Paul Mitchell, before Clive Platt's strike was cleared off the line by Sam Sodje.
But Martin Allen's men battled back in the second half and claimed their fifth win from eight league games thanks to Kevin O'Connor's twice taken penalty in the 62nd minute.
The Dons, missing Gareth Edds and Dean Lewington with injuries picked up in training this week, dominated the early stages and could have gone ahead in only the third minute when Wilbraham's lob came back off the underside of the bar.
The towering striker, who shrugged off a hamstring strain to make the line-up, got the better of Sodje on the edge of the box before lifting the bouncing ball over goalkeeper Stuart Nelson.
Two minutes later ex-Don Marcus Gayle came close with Brentford's first chance, blasting just over from 25-yards after latching onto Jay Tabb's knockdown.
And then Gayle went close again midway through the first half, drawing a good save from Matt Baker with a fierce angled drive.
But Milton Keynes continued to dominate and they hit the woodwork for the second time in the 34th minute when Mitchell's left-foot drive from 20 yards cannoned off the post with Nelson well beaten.
And from the resulting corner after the rebound had been hacked behind, debutant Pablo Mills skewed a great chance wide from 10 yards on his weaker right foot.
At the other end, Baker got down well to save Isaiah Rankin's low strike from the edge of the box.
Milton Keynes striker Platt's effort was then acrobatically headed off the goal-line by Sodje in the 44th minute after substitute Malvin Kamara had pulled the ball back from the by-line.
Brentford, with Allen's words ringing in their ears, stepped it up after the break and they broke the deadlock in the 62nd minute through O'Connor's twice taken penalty.
Leon Crooks was harshly adjudged to have handled Gayle's flick from Darren Pratley's corner and O'Connor rammed home the second spot-kick like he had done the first after the referee had ordered it to be retaken for encroachment.
Substitute DJ Campbell missed a great chance to sew it up by clipping wide when clean through.
At the other end, Kamara wasted a great chance to equalise when he burst past two defenders but dragged his shot wide when one-on-one with Nelson.