A contentious first-half penalty ruined West Ham United's hopes of earning a hard-fought point at Manchester United a fortnight ago.
The Hammers had more than held their own for the opening half-hour at Old Trafford, with both Kieron Dyer and Carlton Cole looking dangerous on the counter-attack.
Both sides came close to opening the scoring in the opening stages, with Robert Green showing outstanding reflexes to push Nani's shot on to the crossbar before Dyer fired a low shot into Edwin van der Sar's side-netting.
However, just when it appeared that Avram Grant's men had weathered the early storm, referee Mark Clattenburg awarded a spot-kick for Jonathan Spector's innocuous-looking challenge on former Red Devils team-mate Ryan Giggs.
Wayne Rooney jinked up to the ball before sending Green the wrong way from 12 yards, netting his first goal since 30 March.
Having gone ahead, Sir Alex Ferguson's team took control of affairs. The England goalkeeper had to be at his very best again to tip Darren Fletcher's shot around the post before Nani wasted a glorious opportunity in added-time, lifting Giggs' pass on to the roof of the net when it looked easier to score.
The Portugal winger made up for his profligacy five minutes after half-time, taking advantage of an unfortunate slip by Danny Gabbidon to race through the middle of the Hammers defence before thumping a shot high into the net from the edge of the penalty area.
West Ham's best moment of the match arrived on 56 minutes, when a sweeping move involving Luis Boa Morte and Julien Faubert ended with Dyer slamming a shot against the outside of Van der Sar's left-hand post - the second league game in succession that the upright had denied the 31-year-old his first Hammers goal.
Having received a let-off, United went in search of a match-clinching third goal and it duly arrived in sensational style with 21 minutes remaining.
John O'Shea and Nani combined down the right before the latter lifted an inch-perfect cross to the far post, where Dimitar Berbatov connected with an unstoppable scissor-kick that flew past Green.
Manager Grant was naturally disappointed to see his team lose their third straight Premier League match, particularly after making such an encouraging start at the Theatre of Dreams.
"Until the penalty we were in the game. Manchester United were not dangerous and we played how we wanted to play. Then they got the penalty but I'm not sure it was a penalty.
"In the second half they scored very early [through Nani] and that made it very difficult. We played against a better team, who were at home. We were fine in the first half but it was different after the second goal and then it became too difficult for us.
"Our first half was good but they dominated the game in the second half. Although we were behind at half-time we were still in the game and we wanted to continue like that."
Midfielder Dyer was equally frustrated by the final result, but believes it will not be long before the Hammers are winning matches again.
"We were disappointed again at Old Trafford. I thought we were fairly comfortable before their first goal. Once Man United are 1-0 up there, it's a hard challenge.
"Man United away is not going to determine how our season goes, but it's another 3-0 loss. It would have been good to get some kind of result just to get the confidence up.
"Obviously last season was a massive struggle but where I'm coming from, for me personally, I'm just buzzing to play football again.
"We've got two weeks now and they've got to get the confidence from somewhere because when we do click and we do get it together, we are not a bad team."