Strikes in the 15th and 17th minutes from Ole Gunnar Solskjaer and Juan Sebastien Veron, plus an own goal from Sebastien Schemmel midway through the second half sealed a scoreline that slightly flattered United, but nonetheless sent them to the top of the Premiership table with Arsenal and sadly left Hammers rooted to the bottom.
Glenn Roeder had made two enforced changes to the team that drew at Middlesbrough last week, as Steve Lomas made a timely return from injury to replace hamstring victim Edouard Cisse, while Scott Minto stepped in at left-back after Nigel Winterburn's late withdrawl with a thigh strain. Young Anton Ferdinand was named as a substitute against his older brother's team, although Rio was still missing through injury.
With Ian Pearce continuing his role as a makeshift striker alongside Jermain Defoe in the absence of Di Canio and Kanoute, it was somewhat of a surprise to see Hammers start the game as much the better side.
Inside the first minute, Roeder's men were denied what looked a decent shout for a penalty, when Defoe cut in from the left and appeared to have his ankles clipped as he burst between two defenders. However, referee Rob Styles, who was well placed, immediately waved away any appeals for a spot-kick.
The visitors continued to enjoy a large amount of possession, though, with Michael Carrick once again shining in the holding midfield role and Lomas and Cole working hard to offer support to the front two.
The early scare clearly provided a wake-up call for United, who began to find their passing rhythm and almost opened the scoring with their first attack of the game when O'Shea flicked on Giggs' corner to bring a superb reflex save out of James.
However, just two minutes later, the opener did arrive. Gary Neville was allowed acres of space to burst down the right and measure a cross to the near post, where Solskjaer's header took a wicked deflection off Repka to deceive an off-balance James and bounce into the corner of the net.
If Hammers found that hard to take, then they were left stunned by United's second, just two minutes later.
After Repka had been booked for a rash foul on Van Nistelrooy some 25 yards out, Veron stepped up to curl a right-footed drive beyond the despairing dive of James and prove you can't afford to gift United free-kicks around the penalty area even when David Beckham is sitting safely on the substitutes' bench.
Giggs almost added an immediate third when he ghosted in to the penalty area unmarked at a corner and guided a left-foot volley towards the bottom corner that James blocked well.
At that stage, many were anticipating a claret and blue collapse, as United's four-pronged attack of Giggs, Van Nistelrooy, Solskjaer and Scholes threatened to run riot. Those who doubted the Hammers were in for a shock, though, as we finished the half on top again and were denied what might have been a crucial lifeline just before the break.
From Lomas' cross wide on the right, United's clearance rebounded off Minto and dropped at the feet of Defoe, who turned in the six yard box and smashed the ball into the roof of the net, only to see his celebrations cut short by the raised flag of the linesman.
TV replays later showed the young striker to be clearly onside when the ball struck Minto, to provide yet more proof that the breaks just don't seem to go our way when they are needed most.
Once again, though, West Ham's response to their misfortune wasn't that of a team lacking in spirit or confidence. Right from the start of the second half, they took the game to their opponents and fought gallantly to inspire a comeback, led by Cole, who almost achieved that aim two minutes after the interval when he burst through on the left and cut the ball back into the danger area, where O'Shea did well to clear for United.
Defoe then saw another half-chance go begging, and United clearly realised that a third goal would certainly be needed to make sure of the victory against their determined rivals.
It should have arrived when Van Nistelrooy was sent clear by Giggs in the 56th minute, but the Dutchman was stopped in his tracks by the lunge of James as he attempted to round the Hammers keeper.
Six minutes later, though, United's clincher finally ended any lingering hopes of a comeback. Gary Neville once again found space on the right and drove in a fierce low cross that flew across the six-yard box and inadvertently struck Schemmel, who watched in vain as the ball ended up in the back of the net.
After enjoying the luxury of being able to introduce the England captain as a half-time substitute, Sir Alex Ferguson then replaced John O'Shea and Paul Scholes with Laurent Blanc and Diego Forlan to add fresh international class for the remaining 20 minutes, while the same 11 Hammers that had started the match battled on bravely.
With most of the 67,555 Old Trafford crowd expecting the hosts to finish with a flourish, it was the visitors who ended as the stronger side and deserved at least a consolation goal for their efforts - as did the tremendous travelling Hammers faithful who had started their journey north at the crack of dawn when many could have opted to watch the lunchtime kick-off from the comfort of their own armchairs.
Scott Minto and Cole both went close to providing a goal late in the game, surging down the left and cutting the ball back only to see Barthez come to his side's rescue, while Carrick almost found the net with a low left foot shot from the edge of the box.
The tireless Lomas - out for more than a month with an ankle injury - finally ran out of steam in the 85th minute and was replaced by John Moncur, while Minto was forced off in the dying moments after his first taste of Premiership action since November 2nd.
The final whistle signalled our ninth successive game without a win, but the performance once again proved that Hammers have what it takes to pull clear of the relegation zone.
Any team hoping for a victory when visiting Old Trafford at the moment will need to hope for an off-day from the Red Devils as much as an impressive performance from themselves, such is the formidable attacking talent currently on song at the Theatre of Dreams, but this display will certainly give Glenn Roeder some heart as we approach the two vital Premiership clashes at Upton Park next week against Bolton Wanderers and Fulham.