Following their UEFA Europa League semi-final success in midweek, Ruben Amorim made six changes to his side, with Mason Mount introduced after his brace, along with Amad Diallo, who was making his first start since early February.
The latter looked his usual dangerous self in the early moments, as he linked up well with Bruno Fernandes only for the Portuguese midfielder to curl his shot over before forcing a save from Alphonse Areola with a more dangerous effort of his own.
The Hammers took until the quarter hour to get going, but when they did, United’s defence looked vulnerable. First, James Ward-Prowse whipped in a curling free-kick into the box which Max Kilman headed over, but that would prove only a temporary reprieve for the hosts.
Ex-United defender Aaron Wan-Bissaka picked out the unmarked Mohammed Kudus on the left, who whipped the ball along the ground to the back post for Tomáš Souček to poke home.
That goal sucked the life out of the United players and Old Trafford, as the hosts trudged their way back into the tunnel for the HT break following a disappointing opening 45 minutes.
Following the restart, the Hammers resumed control of play and very quickly came close to doubling their lead after Kudus’ cutback was hit straight at Altay Bayındır by Ward-Prowse.
Amorim was worryingly forced into a change less than 10 minutes into the second half, as Leny Yoro limped off with a foot injury, while Luke Shaw was also taken off, as Harry Maguire and Victor Lindelöf were introduced.
Those defensive changes had little effect on the Red Devils’ vulnerabilities at the back, with United’s deficit doubled before the hour mark.
Manuel Ugarte was dispossessed in his own half, which allowed Kudus to drive into the box - his shot was deflected into the path of Wan-Bissaka, who slid the ball to the far post for Jarrod Bowen to sweep home.
Amorim’s men finally woke up after falling two behind with Alejandro Garnacho and Rasmus Højlund both going close for the hosts, but as has been the theme of their league season, poor finishing cost United.
The Dane was then sent through on goal by Amad, but his effort from close range was saved by Areola. In the end, Graham Potter’s men saw out the remaining minutes with little trouble, claiming their first victory in nine games to leapfrog United, who slip to an eye-watering 16th as their winless PL run reached a joint-club record of seven matches.
Flashscore Man of the Match: Mohammed Kudus (West Ham United)