Luton's relegation fears were considerably worsened by brilliant Brentford at Kenilworth Road, as Yoane Wissa's first-half double was complimented by goals from Ethan Pinnock, Keane Lewis-Potter and Kevin Schade to secure an impressive 5-1 victory.
The Hatters have four games to rescue their season, starting with a trip to Wolves next weekend, while the Bees have pulled miles clear of the drop zone and can now consider themselves safe - 10 points better off than 18th-placed Luton.
Wissa's superbly-taken opener arrived 24 minutes in, released by strike partner Bryan Mbeumo in the absence of injured Ivan Toney, as he lashed an instinctive first-time effort beyond Thomas Kaminski.
The second was less emphatic but equally important, scored in first-half stoppage time, as Luton's backline went missing to allow Wissa a simple tap-in from close range - upheld by VAR after a brief suspicion of offside.
Pinnock netted Brentford's third from Sergio Reguilon's corner as the visitors' dominance continued throughout the second period, before Lewis-Potter turned home Mbeumo's cross at the back post, and substitute Kevin Schade rounded off a close-to-perfect afternoon - but for a late Luke Berry consolation strike.
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How Brentford ran riot at Luton
Luton had the chance to pull away from the drop zone ahead of Sunday's meeting between fellow strugglers Everton and Nottingham Forest - the points deduction derby.
It was a chance they squandered in quite spectacular fashion.
Brentford, under pressure themselves, inflicted Luton's heaviest home defeat of the campaign, winning back-to-back games for only the second time this term to ease any lingering concerns of being dragged into an unwanted relegation scrap.
Kenilworth Road remained in full voice until the bitter end, undeterred by the scoreline, but Rob Edwards, and his weary players, looked crestfallen. Survival remains an increasingly unlikely uphill task.
With Toney not involved due to his ongoing hip issue, Thomas Frank watched his fluid front four run riot, with Wissa reaching the triumphant total of 10 goals for the season with two commanding strikes before the interval.
Brentford continued to threaten thereafter and only a block by Teden Mengi denied Lewis-Potter after a dangerous run before a sumptuous curled effort from Mbeumo crashed against the crossbar.
Edwards reacted by bringing on Berry - who scored late on - but Brentford's attacking efficiency was ruthless.
A third goal came soon after when Pinnock powered a header home from Reguilon's delivery, and Lewis-Potter got rewarded for his persistence when ghosting in at the back post to steer Mbeumo's knock-on inside the post.
Mbeumo had been first-class and he was again involved in Brentford's fifth after his clever pass found Vitaly Janelt, who set up Schade for a simple tap-in.
Luton's efforts were applauded at the full-time whistle, but their prospects look dimmer by the week. The Bees, however, are now undeniably home and dry.
Frank impressed by 'fantastic' front three
Brentford boss Thomas Frank:
"I have huge respect for Luton, for what they've done, what they are doing. We had to be absolutely on it, super focused. We had to earn the right to attack.
"We defended the box well and we did that fantastically as a team. We ran at them, the front three were fantastic. Even more impressive, not one team has done what we've done to Luton here at Kenilworth Road.
"They have only lost by more than one goal once. That's hugely impressive. It was an important game, because that sneaking feeling [of relegation] is more out of the question. We have to end the season on a high. We want to end unbeaten."
On the fitness of Ivan Toney, Frank said: "We need to get him absolutely right, and fully fit. I thought he would be ready for this game but I strongly believe he'll be ready for Everton."
Edwards apologises to fans: 'We lacked belief'
Luton boss Rob Edwards:
"We had our moments, but we weren't ruthless enough. We lacked an intensity. For the first time this season we showed a lack of belief. We've got to snap out of that really quickly.
"I don't know why. It's hard to put my finger on right now - to lose in that manner is desperately disappointing. I have to apologise to the supporters for having to live through that.
"We've got to respond. I'm apologising, rightly so. It's not been good enough and it's not often I say that. I shoulder it, I'm the manager and have to hold my hands up in these moments.
"We've lost an important game. I'm deflated now, because of the manner of this performance. It wasn't us. I'll have to review the game. We're not out of it.
"As a team we lacked intensity and urgency. I've got to look at that, it's a strange one. We've had that all season, especially at home. Today was a moment to speak how I felt, I didn't rant and rave [in the dressing room]. How I feel is, we're in this, today was just a bad day. We all have to remember that.
"We don't want to give up the Premier League easily."
Opta: Wissa steps up in Toney's absence
- Brentford secured their biggest ever away top-flight victory, netting 5+ goals for the first time on the road at this level (160th such game).
- This was the first time Luton have lost a home top-flight match by 4+ goals since February 1984 (0-5 v Man Utd).
- Yoane Wissa (10 goals in 2023-24) became the first player other than Ivan Toney to reach double figures for goals in a single Premier League campaign for Brentford.
What's next?
Luton head to Wolves on Saturday 27 April, kick-off 3pm.
Brentford face Everton also on Saturday 27 April, kick-off 5.30pm, live on Sky Sports.