It was almost a nightmare start for the Hammers, with Dango Ouattara flashing an effort just wide of the post inside the opening minute.
The dreaded goal came midway through the first half, with Kayode on the scene to help smuggle the ball over the line after it had rebounded off the woodwork. On review, Konstantinos Mavropanos was given the unwanted credit, having been adjudged to have got the decisive touch.
Nuno Espirito Santo’s side produced a strong response, and only the post denied Taty Castellanos an instant equaliser from his clever curling effort.
The visitors then appeared to have got the leveller, with Mavropanos finding the net at the right end this time, but VAR identified a marginal offside to cut short the celebrations.
The Bees should have compounded the Hammers’ misery when Mads Hermansen was left in no man’s land after dashing out rashly, but Mikkel Damsgaard could not find the unguarded net from outside the box.
The woodwork was struck yet again before the break, with Castellanos thwarted for a second time, while Hermansen had to be at his best at the other end to deny Keane Lewis-Potter from close range.
West Ham got off to the worst possible start in the second half, with a rash challenge from El Hadji Malick Diouf gifting Igor Thiago the chance to double the lead from the penalty spot.
The league’s second-highest scorer duly converted, leaving the Irons with a mountain to climb and seemingly draining all the fight out of them, while Brentford settled into a pattern of comfortable control.
A moment of magic from Crysencio Summerville threatened to make things interesting, but the away fans watched in disbelief as his effort found the crossbar once again after a weaving run.
Into the final 10 minutes, Damsgaard settled the issue once and for all, turning sharply in the box before steering the ball into the bottom corner.
The win was just Brentford’s third in their last 16 London derbies, with all of those triumphs coming against today’s opponents.
Victory moves them up to sixth in the table, following Brighton’s loss at Newcastle.
West Ham’s first defeat in four games keeps them firmly mired in the scrap for survival, and Tottenham will get the chance to send them into the bottom three with a win over Aston Villa on Sunday.