Makeshift striker Jay Tabb fired a brace to ease Brentford away from the relegation zone.
Tabb scored his third and fourth goals in the space of four days as the Bees won and end to end thriller at Griffin Park.
Stephen Hunt and Ben May weighed in with a goal a piece to end Luton's three-game winning streak. Adrian Forbes scored two goals for Luton.
Bees manager Wally Downes was pleased with his side's improvement after labelling Tuesday's performance against Barnet in the LDV Vans Trophy a disgrace.
He said: "I don't think we were at our best in the first half, but we stepped it up a bit in the second and were worthy of our victory." Tabb scored two goals in the midweek 3-3 draw before Brentford progressed on penalties and two more goals justified Downes' decision to bring the midfielder on up front after Tommy Wright left the field on a stretcher in the first half.
"He is a bright kid and has a good football brain," said Downes. "He is very determined and it is up to me to keep him progressing along the right lines. He has earned his place in the team now." Dean Brill, Luton's 17-year-old goalkeeper had a nightmare game and was at fault for two goals, but Hatters manager Mike Newell was not pointing any fingers.
He said: "It is only his third game and he did very well in the first two. I am not happy with the way we started and we gave away soft goals.
"We have to go away from home and compete with teams and grind out results." Hunt opened the scoring in the first half when he lobbed Brill from the edge of the area, but the game came to light three minutes after the restart when Forbes finished off a sweeping Luton move with a clinical left-footed strike.
Tabb scored his first after Brill fumbled a long punt forward from Paul Smith and was on hand to tap in from eight yards after good work from May and Hunt.
May prevented him from scoring a hat-trick when he prodded Tabb's goalbound shot over the line before turning villain when he played a dreadful backpass into Forbes' path for Luton's second.