Goals from Robbie Weir and Andy Robinson earned Tranmere their first win at Brentford in eight years and their third victory from the opening five games of the season.
It was a deserved success for Les Parry's side who dominated the game at Griffin Park, creating several decent chances in each half.
Weir's second goal of the season came midway through the first half with Robinson doubling the lead a minute after half time, while Joss Labadie and Martin Devaney also came close to getting on the scoresheet.
There were two changes to the team that started against Sheffield United, with Dave Raven returning from suspension to take the place of Michael Kay at right back and Mustafa Tiryaki coming in for Enoch Showunmi following his midweek hat-trick for the reserves.
An early free kick from Andy Robinson had to be punched away from goal by Brentford keeper Richard Lee, with Robbie Weir volleying over on the rebound.
Weir and John Welsh combined to deny Gary Alexander a shooting opportunity on 11 minuteswhile Weir headed wide from Robinson's corner a couple of minutes later as Rovers made a decent start to the game.
Sam Saunders fired into the Tranmere wall from a free kick and at the opposite end Martin Devaney volleyed past the post as the game remained goalless.
Raven got his head on another Robinson corner on 24 minutes but his effort went well wide of the Brentford goal, but the next time Robinson got a cross in Rovers took full advantage. The former Leeds player got to the goal line on 27 minutes, whipped in a dangerous ball from which Weir send a downward header past Lee and into the net from six yards out.
It wasn't far off 2-0 moments later when Welsh volleyed wide after good work from Devaney and a few minutes later Tiryaki fired over the bar from a free kick following a foul on Welsh 30 yards from goal.
But Brentford's best chance yet came on 38 minutes and the score should have been levelled. A poor back pass from Mark McChrystal gave Clayton Donaldson a one on one chance which needed Owain Fon Williams to produce a decent save. From the resulting corner Donaldson rose highest but his header went over the bar.
Tiryaki brought a comfortable save out of Lee on 40 minutes after good work from Raven and Robinson and the Bees went even closer to scoring two minutes later, with Alexander sending a looping volley onto the cross bar with the ball bouncing behind for a goal kick - the final chance of the half.
Niall McGinn had an early shot seconds into the second half, but before the clock had reached 46 minutes Rovers were 2-0 up. The ball fell perfectly for Robinson 25 yards out and he superbly found the net with his right foot for his first goal of the season.
Tiryaki tried to make it 3-0 with a volley on 48 minutes while Alexander tried to reduce the deficit at the other end moments later with a long range effort that was easily held by Fon Williams.
Saunders looped a shot over the Tranmere bar but it needed a good save from Lee to prevent Tranmere going 3-0 up on the hour mark when Devaney fired goalwards from 18 yards.
Another Devaney effort was kept out following a strong run from Lucas Akins on the right and Akins fired into the side netting himself on 65 minutes.
Showunmi replaced Tiryaki with 25 minutes remaining with Joss Labadie coming on for Robinson soon after.
Labadie brought a save out of Lee with a powerful 30 yard drive on 72 minutes, while cramp forced Akins to be replaced by Zoumana Bakayogo three minutes later.
Fon Williams produced a fine double save to keep out the Bees on 79 minutes , first saving Donaldson's effort before getting up to deny Mike Grella.
Kevin O'Connor miss hit a shot on 89 minutes while a free kick for a foul on Bakayogo gave Rovers a promising shooting opportunity at the other end as the game approached injury time but Labadie's attempt struck the wall.
Brentford: Lee, O'Connor, Legge (Eger 56), Osborne, Woodman, Saunders (Grella 65), Douglas, Reeves (Bean 45 HT), McGinn, Donaldson, Alexander. Substitutes not used: Moore, Weston.
Tranmere: Fon Williams, Raven, Goodison, McChrystal, Buchanan, Welsh, Weir, Robinson (Labadie 68), Akins (Bakayogo 75), Tiryaki (Showunmi 65), Devaney. Substitutes not used: Coughlin, Kay.
Referee: David Phillips
Yellow cards: Tiryaki (32), Osborne (33), Saunders (53), Devaney (61), Douglas (73), Bakayogo (77), Bean (85), Weir (90+2)
Follow Tranmere on Twitter at www.twitter.com/tranmererovers.