Ole Gunnar Solskjaer rolled the dice for the second time in a week – and once more came up trumps.
The Old Trafford chief sparked a second-half revival on the south coast at Southampton and thought he'd try his luck again in the East End.
Last week, it was Edinson Cavani who made the difference – this time out he made a double-switch, bringing on Marcus Rashford and Bruno Fernandes at the break after the game appeared to be slipping from his grasp.
And their introduction was the catalyst for Paul Pogba, Mason Greenwood and Rashford himself to grab the goals to put the brakes on the Hammers' charge up the Premier League table.
David Moyes' side had been full value for a half-time lead, an advantage given to them when Tomas Soucek bundled home from close-range.
The visitors, who went up to fourth with this win, were staring at a deserved deficit at the interval but at least they did not appear to be cut adrift as they had been against Ralph Hasenhuttl's side.
It took a spectacular turnaround to drag that result out of the fire and it looked like something similar was needed to stop the in-form Eastenders from grabbing victory.
However, it took a controversial goal to start the comeback. Dean Henderson's long punt down the right flank was picked up by Bruno Fernandes.
Moyes immediately claimed the ball had gone out of play but VAR sided with the on-field decision. Fernandes's cross was sidefooted home beautifully by Pogba from 20 yards out and the fightback began.
Greenwood then swivelled and added a second with the hosts still reeling from the first blow and then Rashford sprinted clear to put the result beyond doubt for the third.
Solskjaer had made four changes following the midweek defeat to Paris St Germain, the most interesting of which was Pogba's recall with Fernandes dropping to the bench.
David de Dea was omitted from the squad altogether with Henderson taking his place and a rare outing for fourth-choice keeper Lee Grant.
There has been precious little love lost between these two clubs and there was a decided air of anticipation in the air when the match got underway with those 2,000 fans present acting as if they would with a far larger throng in attendance.
It was Jarrod Bowen who caused the first stir. Cutting in from the right, he found Henderson blocking his path to goal. A few moments later, he managed to beat the Manchester United shot-stopper, only to see the assistant's flag pull him up for offside.
After half-an-hour it was clear that West Ham were feeding off the 2,000-strong crowd's energy. Solskjaer's men had shown flashes without creating anything clear-cut.
Up at the other end, though, it was a different story.
Two chances fell to Pablo Fornals within three minutes, Tomas Soucek scored the opening goal and Sebastien Haller rounded the keeper – only to lose his footing with the goal at his mercy - and only a last-gasp Victor Lindelof block prevented Fornals from finally breaking through.
Moyes would have been happy with a half-time lead. But miffed it wasn't more.
Fornals' first chance saw him plant a header into the side-netting after good work from Bowen.
Then, after Haller laid a ball into his path, the Spaniard toe-poked a shot past Henderson only to see it roll into the foot of the post and bounce back into the grateful keeper's arms.
The opening goal showed yet more deficiencies in the United defence. Aaron Cresswell's near-post corner was flicked on by Declan Rice - under no pressure – and the Czech international bundled home.
It was deserved too. Seconds later Haller, who galloped straight down the middle after Victor Lindelof squandered possession cheaply on the halfway line, fell at the final hurdle after racing clear down the middle.
Solskjaer was clearly unhappy with what he had witnessed and made changes. Although there had been flashes, most notably when Scott McTominay fired wide, the goal that levelled was special.
It was to rock the hosts. Greenwood was deadly with his left foot moments later and Rashford's third, sprinting clear wrapped up the points.