Brentford took advantage of a much-changed West Ham side to claim a comfortable 2-0 home win that guarantees them a top-half Premier League finish.
The Bees, who were missing star striker Ivan Toney due to a minor hamstring issue, scored twice in the first half through Bryan Mbeumo (20) and Yoane Wissa (43).
Thomas Frank's side had 24 shots against West Ham, who made nine changes with one eye on Thursday's Europa League Conference semi-final second leg against AZ Alkmaar in the Netherlands.
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One of those changes was Danny Ings and he was denied a second-half goal by VAR for a handball in the build-up to his close-range header that would have given West Ham a route back into the game. It was a decision that Irons boss David Moyes later labelled "very strange".
The Hammers are all but safe in the Premier League as they sit six points above the drop zone, although a win in west London would have mathematically secured their safety.
Brentford, meanwhile, have now won all four Premier League meetings against the Irons in a victory that moves them up to ninth above west London rivals Fulham.
Makeshift Irons punished by dominant Bees
The team news at the Gtech Community Stadium showed West Ham's priorities clearly lay elsewhere with David Moyes putting out a makeshift team ahead of Thursday night's trip to AZ Alkmaar.
But it was one of the two players that kept their place from the first-leg win over AZ that allowed Brentford to open the scoring in the 20th minute.
Defender Nayef Aguerd's sloppy pass was intercepted by Mikkel Damsgaard, with the ball eventually falling to Mathias Jensen, who teed up Mbeumo to fire low under Lukasz Fabianski.
The Hammers goalkeeper may have been at fault for the opener but he made up for it as he denied Wissa twice, with the second save coming amid a chaotic goalmouth scramble that ended with Ben Mee seeing his smashed shot deflected behind.
Wissa, however, did get the better of Fabianski in the 43rd minute. A Jensen long throw was flicked on by Mee for Wissa to head in for his sixth goal of the season.
Further chances followed in the second-half for Brentford to finish the game off but Wissa, Mbeumo and Damsgaard all missed.
Moyes sent on Declan Rice and Said Benrahma with half an hour left and the latter nearly kick-started a Hammers comeback.
The ex-Brentford player's cross crashed off the woodwork into Manuel Lanzini's path and he clipped a ball into Ings who headed in.
But the goal was disallowed by VAR as substitute Divin Mubama was adjudged to have handled after the ball rebounded onto his arm off the post.
Moyes questions 'very strange' VAR decision to disallow Ings goal
West Ham manager David Moyes speaking in his post-match press conference on the decision to disallow Ings' header:
"Very strange. The Premier League have come out and called it deliberate handball. I think we need a bit of explanation on that.
"The first thing I would say about it is, it is inconclusive. If anything I think it hits his shoulder, right on his collarbone.
"If it's a handball that leads to a goal we all know that rule, but I certainly don't see deliberate. If anything he might be protecting himself from going into the post. I'm amazed it was chalked off.
"But, let's be fair, if this was the first one we were talking about in recent games I would say it can happen, but we're now talking about three of these [after being denied penalties for handballs against Liverpool and Manchester United in recent weeks].
"It's getting regular. It really is. I don't want to get in trouble but we've had three real ones that could have altered things, and if you said we've had our fair share, I'm saying I don't think we have."
On the defeat: "I didn't enjoy the performance. I thought we were soft, easy to play against. It was so poor.
"We did some work on defending long throws, but you wouldn't have thought it watching that today. I'm so disappointed the players didn't deal with it."
Frank: Top-half finish a 'brilliant achievement' | Toney
Brentford head coach Thomas Frank speaking in his post-match press conference on guaranteeing a top-half finish:
"I was asked before the season about that, and without sounding too smart we tried to analyse things, looked at the players, the other teams, our performances, our culture, and we thought why shouldn't we be able to do well in our second season?
"Now we are 100 per cent in the top 10, which is a brilliant achievement."
On Toney's hamstring injury, Frank added: "We'll assess him during the week and, hopefully, he's going to be available for Tottenham. That's what we're working towards."
What's next?
Brentford now face two of the 'Big Six' in their final games of the season, travelling to Tottenham next Saturday lunchtime before hosting Manchester City on the final day of the season on May 28.
West Ham's attention turns to the second leg of their Europa Conference League semi-final away at AZ Alkmaar on Thursday night, before they host Leeds next Sunday, live on Sky Sports with kick-off at 1.30pm.
The Hammers' final league game of the season is away at Leicester on May 28.
Opta stats: Hammers away woes worsen
- West Ham have lost 12 away games in the Premier League this season - their joint-most across a single campaign in the competition. The Hammers last lost more such matches in a league season in 1991-92 (13).
- Brentford are unbeaten in their last eight London derbies in the league (W4 D4) - this is the Bees' longest run without defeat against fellow London opponents since August 1955 (a run of 11).
- West Ham have lost eight of their last nine league London derbies away from home - with their only such victory across that run coming at Fulham in April.
- Brentford have scored 33 goals from set pieces over the last two Premier League campaigns (excluding penalties), while only Liverpool and Manchester City have netted more in that period (both 36).