Former United striker Danny Welbeck's second half winner knocked ten man United out of the FA Cup and put the Gunners into the last four.
Nacho Monreal put the visitors ahead just before the half-hour but Wayne Rooney's superb equaliser pulled the Reds level only for Welbeck, and several questionable refereeing decisions, to end our Cup dream.
Although Arsenal probably deserved the win, United will be left with a lingering sense of injustice after Angel Di Maria's harsh sending off and the denial of at least one strong penalty appeal.
United started well and went close early on through Ashley Young's well hit effort and Marouane Fellaini's half chance when he failed to get the ball out from under his feet and Arsenal cleared.
The revitalised Di Maria was denied by an excellent save from Wojciech Szczesny but it was Arsenal who went ahead on 26 minutes when Alex Oxlade-Chamberlain's trickery allowed Monreal to pick his spot and the full-back steered in a controlled finish.
United were not behind for long though and quickly restored parity when Di Maria's inch perfect cross from the right was nodded home by a stooping Rooney from close range.
Rooney lashed narrowly over the bar and Di Maria also went close from Fellaini's pull back before Arsenal went ahead against the run of play in catastrophic fashion.
Antonio Valencia's underhit backpass sold David de Gea short and the predatory Welbeck reacted quickly to nudge the loose ball around the stranded keeper and roll into the unguarded net.
Welbeck, who made nearly 150 appearances for United, later departed to a largely rapturous welcome but United were almost 3-1 down by then as De Gea somehow clawed out Santi Cazorla's shot from an Alexis Sanchez cross.
Di Maria was then sent off in a confusing passage of play when a trip on the Argentine was interpreted as a dive, earning him a yellow card and he was then sent off for placing his hand on the referee's shirt in an attempt to attract Michael Oliver's attention.
Hector Bellerin then somehow escaped punishment when, having already been booked, he clattered into Ashley Young but remained on the field.
United then had a penalty appeal waved away when Adnan Januzaj was pulled down by Per Mertesacker, but the youngster was harshly booked.
De Gea made another miraculous save to keep out Sanchez and Rooney went close with a late effort as the Reds fought until the death but our task now is to refocus on the top four challenge that lies ahead.
United Faithful Man of the Match: Wayne Rooney
Overall team performance: 7/10