The Mariners, with an outside chance of the play-off before kick-off, led 1-0 at the break, but never got going after that and the combination of missed chances and shoddy defending contributed to the defeat.
The Bees were there for the taking, but in the end the Londoners were worth their win, which atoned for the home defeat by Grimsby back in December.
It was a low-key match throughout with an above average crowd not being able to lift the side and vice-versa.
After striker Danny North had wasted a great chance when he should have played in Jamie Clarke, the striker stooped to glance home his tenth goal of the season from a cross by wing-back Nick Hegarty.
This goal came in the 18th minute and Grimsby could have been further ahead with Peter Till having a shot beaten away by the keeper and then heading over from another cross by the impressive Hegarty.
But, just as they had done on so many occasions this season, Grimsby conceded an early second-half goal. Striker Alan Connell nodded in from a Craig Pead cross and the equaliser breathed new life into the visitors.
Apart from a great chance which centre-back Ryan Bennett should have buried and an effort from Hegarty, which was well saved by Simon Brown, it was Brentford who dictated the second half.
But when the winner came on 82 minutes from sub Wayne Brown it stemmed from a terrible ball by Ciaran Toner which gifted Brentford possession.
With men to spare, the ball eventually reached the sub, who took his goal well with a low shot into the corner.