Bees manager Leroy Rosenior was also dismissed, ordered to the stands after 70 minutes when he leapt out of the dugout to complain about a string of controversial decisions from referee Clive Penton.
Brentford striker Chris Moore saw red for a two-footed challenge, even though he appeared to win the ball, while Luton defender Leon Barnett completed Penton's hat-trick when he was sent off for a professional foul on Jo Kuffour.
The decisions overshadowed a professional display from Luton, who won comfortably with goals from Dean Morgan, Warren Feeney and Rowan Vine.
Brentford had the first chance of the game and came mighty close to taking the lead after seven minutes.
Top scorer Kuffour forced a fine save from Town goalkeeper Marlon Beresford when he latched onto a Paul Brooker cross - and then Thomas Pinault's thunderous follow-up effort from 25 yards crashed against the post.
Luton took full advantage by grabbing the lead with their first meaningful attack in the tenth minute, strolling through a non-existent Bees defence for winger Morgan to calmly stroke the ball home left-footed from inside the box.
Morgan was the visitors' most lively player and had another good effort saved, while Feeney missed a wonderful chance when he dinked his shot straight at keeper Stuart Nelson.
Brentford had plenty of the ball in the first half and several chances to equalise. Not least when Simon Cox struck a ferocious 30-yard effort that narrowly cleared the bar.
Luton, however, dominated the second half and effectively clinched victory when Feeney slid home the ball unmarked at the far post after 53 minutes.
Brentford had appeals for a penalty turned down after Kuffour was upended in the box on the hour, effectively ending their challenge.
The match took a turn for the worse when referee Penton completely lost control in the latter stages.
Rosenior was sent to the stands and was followed off by Moore, who appeared to have done little wrong.
It was no surprise when Penton evened things up by sending off Barnett for impeding Kuffour as he bore down on goal five minutes from time.
Brentford battled hard to try and get back into the game, but Luton sub Vine completed a comfortable victory for the Hatters with a fine run and slide-rule shot in the 90th minute.