Reds were undone by two goals from Clayton Donaldson as they suffered their first away defeat in League One since the opening week of the season.
Donaldson struck in either half after Nicky Adams had nudged the ball over the line to level for Reds just past the hour to register his third goal in a week.
The visitors were indebted to keeper Paul Jones for some fine first-half saves but rallied after the break and were in the ascendancy when the Bees got their second.
The defeat means Reds drop three places to sixth ahead of a return visit to Griffin Park on Tuesday in the second round of the Johnstone’s Paint Trophy.
Richie Barker had made two changes to the side that beat Bournemouth in midweek with Jonathan Forte getting his first League One start up front in place of Nicky Ajose while Kyle McFadzean returned in central defence after three games out with a hip problem in place of Claude Davis (thigh).
Brentford have a formidable home record and it was easy to see why as they soon began to dominate the visitors.
Harry Forrester had the ball in the net after six minutes when Donaldson played him in but the offside flag was raised.
Jones then came to Reds’ rescue with three fine saves in seven minutes. On 13 he parried Paul Hayes’ shot at close range for a corner which Donaldson met only for Jones to push his header onto the post.
Jones then got behind a long-range effort from Shaleum Logan on 20 minutes, by which time Brentford had already won six corners.
Reds were just a sporadic threat on the break and it was no surprise when the hosts went in front on 24 minutes, the impressive Forrester sliding a pass down the side of McFadzean and DONALDSON nipped in to lift it over Jones and into the corner of the net.
Jones made another good save when he kept out Forrester’s free kick then McFadzean slid in to take the ball off Donaldson’s feet otherwise the Bees’ striker would have had a second.
Reds finally began to get a toe-hold in the game towards the end of the first half. Nicky Adams fired over from the left-hand corner of the box and in stoppage time Nathan Byrne’s inviting centre was met by Gary Alexander, but he couldn’t keep his header on target.
There was no surprise given our record in the second half of away game this season that there was a dramatic improvement after the break.
On 52 minutes Alexander’s pass fed Akpan who burst into the box but saw his curling shot saved by Simon Moore.
Jones still had to be alert and he turned over Donaldson’s close-range header five minutes later but momentum was building in the other direction and Reds drew level just past the hour.
Logan's attempted back pass was intercepted by Forte and he somehow managed to nudge the ball along the goalline from an acute angle and ADAMS bundled it over the line – a great moment for him against a club he once had a loan spell with.
Five minutes later Forte’s pass inside the box found Akpan but his shot was again superbly saved by Moore and at that stage it looked like it would be Reds who would go on to take the points.
Instead the hosts re-established their lead in the 77th minute. Jones came to the edge of his box to try and clear but Donaldson instinctively lifted the ball over the keeper and had a free run on goal and a tap-in for his second of the game.
It was harsh on Reds and as they went for an equaliser Moore rescued Brentford with a wonderful tip-over from substitute Billy Clarke’s free kick. Clarke had another chance deep into stoppage time, after Kyle McFadzean was tugged on the edge of the box, but he failed to keep his effort on target.
With three subs already on, Brentford finished the game with ten men after Farid El Alagui was stretchered off but the home side clung on to the three points that they deserved.