The visitors had hung on gamely for much of the match and defended well but Brentford eventually made their domination count and never looked like losing after they went ahead.
The first goal came in stoppage time at the end of the first-half when a near post run by central defender Karleigh Osborne went unchecked and he powered home a Kevin O'Connor corner.
Port Vale may have felt aggrieved as the fourth official indicated one additional minute and it was well into the third when the ball hit the net but it was no more than Brentford deserved.
They should have been ahead inside five minutes when Marvin Williams won a penalty after he was tripped by Gareth Owen.
Top scorer Charlie MacDonald stepped up to take the spot-kick but Vale keeper Joe Anyon got down well to his right to save.
For much of the match Brentford ran their visitors ragged, a second goal was always likely.
It came late on when substitute David Hunt and MacDonald combined. The former saw his shot saved but MacDonald forced home the loose ball to seal the win.
It could have been more, Williams forced Anyon into a good low save and MacDonald fired into the side netting.
MacDonald also had an acrobatic effort well blocked and Jordan Rhodes headed wide when well placed.
Vale's attacking play was limited to sporadic forays forward and half chances.
Brentford goalkeeper Ben Hamer saved well from a Scott Brown shot and Simon Richman went close from a corner, but his shot was blocked by a combination of the home defence and team mate Louis Dodds.