David Mooney's second-half penalty and a late strike from substitute Shaun Batt saw Orient extend their lead at the top of League One to five points.
Russell Slade's men met their match against last season's play-off finalists in a closely contested first half, but they upped the tempo after the interval.
It paid off after 65 minutes when Mooney was fouled by Shaleum Logan and picked himself up to score from the spot, making it eight goals for the season.
Brentford boss Uwe Rosler made a trio of changes within 10 minutes of falling behind, with attacking reinforcements arriving in the shape of Stuart Dallas, Marcello Trotta and Joao Teixeira.
But it was an Orient substitute who had the final say as Batt, on for the experienced Kevin Lisbie just three minutes earlier, latched onto Moses Odubajo's pass before steering past Richard Lee.
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