The Hammers stunned the Theatre of Dreams with Diafra Sakho's opener two minutes in, before Zlatan Ibrahimovic equalised in the 21st minute. Jose Mourinho's dismissal was sandwiched between chances from Marcus Rashford, Ibrahimovic and Jesse Lingard to round off an eventful first period.
It took a while for the second period to get going, but decent opportunities for Henrikh Mkhitaryan, Paul Pogba, Ibrahimovic and Ashley Fletcher followed, but could do nothing to change the scoreline.
Straight out the blocks
Both side's headed into this contest in desperate need of points, with United looking to ignite their European challenge, and the visitors looking to distance themselves from relegation zone.
Slaven Bilic's side started the brightest, but nobody would have expected to take the lead with 120 seconds on the clock. It was simple football from, the Hammers, with Dimitri Payet whipping in a free-kick for the returning Sakho, who got ahead of Ibrahimovic to nod home from six yards.
Back in the contest
The goals seemed to shock United into life, and it wasn't long until they found themselves back on level terms. Ibrahimovic marked his return to the league with style, getting beyond James Collins to nod home Pogba's perfectly weighted ball over the top.
United began to dominate from that point as they look to get their second, and had some decent opportunities to do so.
The first came in the 37th minute, as Rashford to end his mini goal drought, and it looked like he would having put through on goal, but Darren Randolph saved with his leg.
Mourinho missed the next opportunity just before the break, seemingly been sent to the stands once again. The manager's absence didn't seem to distract Pogba as he slid the ball through to Ibrahimovic, with the Swede certain to score, but Angelo Ogbonna did brilliantly to throw himself in to block the danger.
Randolph was called upon once again in first-half stoppage time. United were cutting through the West Ham defence with ease, with Lingard in on goal but Randolph did well to turn his near-post effort away.
Took a while to get going
The second-half certainly didn't start like the first, with Payet's 55th-minute effort anything of recognition, but the game burst into life as the game entered the final 13 minutes.
Mkhitaryan was looking to continue to impress Mourinho, and the Armenian almost did that as he poked the ball goalwards from six yards. Randolph had been brilliant so far, and was there again to turn the effort onto the post.
The Irish international was there once again just moments later, as Pogba tried one from 25 yards. The Frenchman's effort looked to be creeping into the bottom corner, but Randolph was there once again to thwart the Red Devils.
Right at the death
The home side began to turn the screw, as they desperately looked for the winner with time against them.
They had another opportunity in the 81st minute, when Wayne Rooney chipped a ball into Ibrahimovic, with the Swede hitting a volley back across goal but Randolph saved well once again.
However Bilic's side almost gifted the points a minute later, with Collins' backpass too short which allowed Ibrahimovic to nip in, but his touch was against him on that occasion.
The final chance of the afternoon fell to a familiar face of the Old Trafford faithful, with Fletcher returning to his former home for the first time since his summer move. He almost came back to haunt his previous club, as he wriggled through a couple of challenges but his effort was straight at David De Gea.