A David Mooney penalty and late goal from substitute Shaun Batt sealed Orient's eighth win from as many games this season, claiming back their five point lead at the top of the table.
It was a brilliant team display from the O's who showed great grit and determination to seal the win in a game that could easily have swung the other way.
A defensive masterclass from captain Nathan Clarke and his colleagues ensured they were always in with a chance of snatching victory, especially with a strike force as potent as the O's has been this season.
The away side had to hold out until 65 minutes before gaining the lead when Mooney coolly converted the penalty he had just won and they remained solid thereafter too, allowing Batt to race away and put the game beyond doubt with five minutes left.
Russell Slade named an unchanged XI from the side that thumped Notts County 5-1 in their last outing just under a week beforehand, while Brentford brought Martin Fillo in to replace George Saville after their dramatic win over Tranmere Rovers last week.
The first opening of the game came after three minutes when a long ball forward down the left was scrappily won by Mooney and his strike partner was first to the knockdown, but Lisbie's volley went high and wide of the Bees target.
Soon after, excellent play down the opposite flank saw Lloyd James create an opportunity for Mooney but his shot was excellently blocked by the home defence.
Despite lining up at centre-back for the home side, Harlee Dean was turning out to be Brentford's biggest threat going forward in the early exchanges - first heading a free-kick just wide of the target and soon after embarking on a marauding run through the heart of the O's defence which ended in penalty claims from the hosts but referee James Linington waved the protests away.
Moses Odubajo looked as lively as ever for the O's firing just over before delivering a fine cross for Mooney, who was unable to keep his headed effort down.
Brentford were edging the midfield battle in the first half with their narrow quartet preventing James and Romain Vincelot from being as effective on the ball as they have been of late, meaning the O's struggled to maintain enough possession to force the home side back.
Jamie Jones was having a busy opening period but looked particularly alert to any danger, comfortably holding on to several decent efforts from Brentford - most notably striker Clayton Donaldson's dipping shot from 20 yards after a spell of good pressure from his side.
It was a half of few openings for both sides with neither team able to stamp their authority on proceedings, and it was the home side who seemed to let this frustrate them the most as they began to knock the ball long to Donaldson in the hope their striker could out-muscle Orient's centre-half pairing.
However the Bees front man found himself faced by two defenders, in the shape of Clarke and Mathieu Baudry, who have been in formidable form this season and were in no mood to let that change tonight.
Orient did manage to craft out a couple of openings at the other end as the break approached but an off-target effort from Kevin Lisbie and Mooney apiece confirmed it would be a first-half stalemate.
A lively opening to the second period saw the home side come nearest to taking the lead through an unusual source. A free-kick whipped in from diminutive midfielder Adam Forshaw flashed across the Orient box before being met by the outstretched leg of Vincelot and the Frenchman's intervention almost saw the ball end up in his own net.
Orient had to withstand a barrage of balls into their box shortly after this. However the away side's defence stood firm - a heroic challenge from Clarke and continued safe hands from Jones being the biggest contributing factors.
And this resilience at the back paid off on 65 minutes when Mooney broke into the opponent's area before becoming engaged in a tussle with Brentford's Shaleum Logan.
The fullback was adjudged to have pulled down the O's top scorer and Mooney himself stepped up to confidently slot the penalty home to move him on to eight league goals for the season.
The spot-kick was right under the nose of Orient's 893 travelling fans and they silenced the home crowd with their euphoric celebrations.
Odubajo might have doubled the lead less than two minutes later when he cut inside onto his left foot but his powerful effort narrowly evaded the crossbar.
Brentford rang the changes in response to the O's goal - making three attacking substitutions in the space of eight minutes - and they continued to pose a threat when they worked the ball wide but struggled to find a way past a solid visiting backline.
And with just five minutes left on the clock, amid chants of "we are top the league" from the Orient faithful, the away side broke down the right flank to extend their lead.
Odubajo, looking every bit as energetic as he did in the opening five minutes of the game, darted inside with the ball before sliding a perfectly weighted, defence-splitting pass through to substitute Shaun Batt who remained calm enough to slot a side-footed shot past goalkeeper Richard Lee to put the game to bed.
It may not have been the most dominant of displays from Slade's men this season but it was a textbook away performance which saw them cope admirably with the home side's pressure and capitalise on the few chances they managed to carve out.
BRENTFORD: Lee, Forshaw, Craig, Dean, Donaldson, Grigg (Trotta, 75), McCormack (Dallas, 77), Logan, Fillo (Teixeira, 69), Diagouraga, Taylor.
SUBS: O'Brien, O'Connor, El Alagui, Reeves
BOOKINGS: Diagouraga (53), Logan (65), Dean (88)
ORIENT: Jones, Omozusi, Clarke, Baudry, Cuthbert, Cox, James, Vincelot, Odubajo, Mooney (Bartley, 88), Lisbie (Batt, 82).
SUBS: Larkins, Sawyer, Lasimant, Gorman, Stockley.
GOALS: Mooney (65), Batt (85)
BOOKINGS: Baudry (72), James (78), Cox (89)
ATTENDANCE: 6,439 (893)
REFEREE: J Linington