A goal in each half from Kevin O'Connor and a late strike from Marcus Bean gave Brentford a 3-0 win at Prenton Park in npower League 1.
The visitors took the lead from the penalty spot and added their second direct from a free kick on a frustrating afternon for Rovers.
Dale Jennings and Lucas Akins went closest to scoring for Les Parry's side and a Showunmi effort was ruled out, but the Brentford keeper was never overly tested throughout the 90 minutes.
There were two changes to the side that started at Southampton as Ian Goodison returned from suspension and Liam Darville came back from injury with the pair taking the places of Nick Wood and Max Blanchard respectively. Adam McGurk was passed fit enough for a place on the substitutes' bench.
Brentford's Charlie MacDonald had the ball in the Tranmere net on five minutes but the effort was ruled out for a foul in the build up.
However, the visitors were awarded a penalty two minutes later. A cross from MacDonald was floated across the area and as Aaron Cresswell challenged Gary Alexander for the ball it struck an arm and the referee pointed straight to the spot despite protests from the home players. Peter Gulacsi dived the right way to Kevin O'Connor's spot kick but there was enough power on the shot to put the Bees a goal up.
Dale Jennings and Cresswell linked well on the left on 15 minutes with the former running between two defenders and into the area only to see his cut back across the six yard box cleared by the Brentford defence.
Gary Alexander fired over from close range after Michael Spillane did well to keep the ball in play from a free kick while Jennings raced back to cut out another Bees attack on 20 minutes, winning the ball from Alexander before clearing the danger.
Arnaud Mendy went down in the Brentford area after receiving the ball from Lucas Akins but penalty appeals were waved away and Jennings dragged a shot wide from 12 yards after running on to Akins' flick on from a Darville cross.
Jennings sent a powerful shot just wide of the left hand post from 25 yards on 32 minutes and Akins just failed to connect with Enoch Showunmi's curling cross at the far post soon after as Rovers pressed for an equaliser.
More penalty appeals were rejected when Michael Spillane made a last ditch tackle to prevent Jennings from a free run on goal but appeared to land on the ball with his arm in doing so.
A cross from Cresswell was caught by Brentford keeper Ben Hamer on 43 minutes while Darville cleared at the other end after Wootton's slip allowed Alexander to send the ball along the six yard box.
A good run from Jennings saw him get past the right back but his cross was turned behind by Leon Legge, while a slip from Goodison gave Alexander a shooting opportunity on 52 minutes but Cresswell blocked and the Brentford striker sent the rebound well over the bar.
Showunmi headed wide Cresswell's cross on 54 minutes from a central position six yards out and the striker fired over the bar a couple of minutes later when a pass to Jennings may have been a better option.
Showunmi raced towards goal before seeing his low shot saved by the feet of Ben Hamer on 58 minutes and Goodison did well to get on the end of a Cresswell free kick but his header went wide of the target.
Akins sent a 25 yard shot just past the top left hand corner after Showunmi held the ball up on the right wing on 65 minutes, while Ryan Fraughan replaced McLaren before the goal kick could be taken.
However, the young midfielder hadn't had chance to touch the ball when the visitors went 2-0 up, as a long range free kick from O'Connor bounced through the Rovers area and straight in at the far post.
More penalty appeals were turned down soon after Brentford's goal when Showunmi went down during an aerial challenge, while Sam Morrow replaced Akins in another attacking change.
With Rovers throwing men forward Brentford killed off the game with ten minutes remaining, Marcus Bean advancing into the six yard box to sidefoot home a low cross.
Fraughan sent a 25 yard shot wide in the final minute of normal time, the final effort of the game for either side.
Tranmere: Gulacsi, Darville, Wootton, Goodison, Cresswell, Mendy, McLaren (Fraughan 65), Welsh, Akins (Morrow 72), Showunmi, Jennings. Substitutes not used: Collister, Wood, Bakayogo, Blanchard, McGurk.
Brentford: Hamer, O'Connor, Woodman, Bean, MacDonald, Weston, Spillane, Wood, Osborne, Alexander (Grabban 84), Legge. Substitutes not used: Lee, McCracken, Balkestein, Saunders, Hunt, Diagouraga.
Referee: David Webb
Yellow cards: Darville (19), MacDonald (68), Alexander (78)