Goals either side of the break from Marcello Trotta and substitute Will Grigg kept the Bees ahead of Lonson rivals Leyton Orient despite being without four regulars through injury.
Vale had goalkeeper Chris Neal to thank for keeping them in the game with two breath-taking second-half saves to keep out long-range shots from Trotta and Clayton Donaldson.
New signing Alan Judge stung Neal's fingers with two dipping drives before Trotta gave the hosts the lead on the half-hour mark, turning on the edge of the box to rifle home into the bottom corner.
Donaldson thought he had sealed the points in the 60th minute when he got above Neal to head home, but the effort was ruled out to the anger of the Griffin Park crowd.
Brentford made sure of maximum points late on as the Londoners broke quickly and Jake Bidwell's left-wing cross found Grigg unmarked in the middle and the striker drilled home from 12 yards.