Luton moved into the Carling Cup third round after a fiery contest in which both sides had a man sent off.
Brentford looked more likely to take the lead when Simon Cox hit the post but Dean Morgan then put Luton ahead.
Wayne Feeney tapped home to make it 2-0 after 53 minutes and things got worse for the Bees when Chris Moore was sent off for a lunging tackle on Rowan Vine.
Luton's Leon Barnett was then dismissed for a rash foul on Calum Willock before Rowan Vine scored to complete the rout.
Brentford: Nelson, Osborne, Heywood, Mousinho (Willock 56),
Charles, Brooker, Pinault, Cox (England 90), Tillen, Kuffour,
Tomlin (Moore 68).
Subs Not Used: Masters, Carder-Andrews.
Sent Off: Moore (80).
Booked: Pinault, Cox, Osborne.
Luton: Beresford, Brkovic (Foley 89), Barnett, Keane, Edwards, Bell, O'Leary, Holmes, Morgan (Langley 90), Feeney, Boyd (Vine 75).
Subs Not Used: Brill, Stevens.
Sent Off: Barnett (88).
Goals: Morgan 10, Feeney 53, Vine 90.
Ref: C Penton (Sussex).