Tranmere Rovers were handed the initiative as early as the 12th minute when Brentford striker Peter Beadle was red carded for elbowing Gareth Roberts and the Wirral side went on to win comfortably, aided by two penalties.
Rovers were ahead after 22 minutes from a Gary Jones header following a cross from Shane Nicholson.
They doubled the lead on 38 minutes. Nicholson sent keeper Paul Smith the wrong way with a left foot shot into the corner after Ibrahima Sonko conceded a penalty for a needless foul on Micky Mellon.
The Bees did not manage a shot on target in the first half but in the 58th minute Jay Smith saw an effort stopped at the second attempt by keeper John Achterberg, who went on to turn aside a well struck free kick by Michael Dobson three minutes later.
Brentford were handed a lifeline in the 64th minute when Achterberg gave away a penalty for a push on substitute Jay Tabb. Steve Hunt fired home left foot into the left corner.
But Rovers soon took control again when Simon Haworth headed in at the far post from a Nicholson free kick in the 76th minute.
Then in the 80th minute Nicholson scored his second after Leo Roget impeded substitute Eugene Dadi.
Brentford boss Wally Downes was furious about the dismissal: "It was never a second off. I saw the incident. The referee said my player elbowed their man in the face but it was not the case and was a completely wrong decision.
"It was 100 degrees out there and we had to play with ten men. You cannot point the finger at anyone for the defeat." Tranmere manager Ray Mathias said: "I have got to be very pleased although we took our foot off the gas a little after half time. Brentford did not die easily and made it difficult for us.
"It was not easy in the searing heat and I have got to be pleased with our work rate generally."