Former Manchester United striker, Danny Welbeck was on hand to send his boyhood club out of the FA Cup in his first return to Old Trafford after leaving for Arsenal.
Arsenal manager Arsene Wenger chose to start Welbeck in place of Oliver Giroud and England forward paid back his boss support with a second half goal to send the club through to the semi-finals of the FA Cup.
The FA Cup defending champions faced an uphill task facing Manchester United in Old Trafford at the quarter-finals; the Gunners had not not won at the ground since Emmanuel Adebayor's goal in a 2006 premiership clash.
Arsenal opened scoring through their Spanish left back Nacho Monreal.
The goal came midway through the first half as Alex Oxlade-Chamberlain weaved his way through the United defence before teeing up Monreal to coolly slot his close-range shot past a diving David de Gea and into the bottom corner.
Manchester United responded immediately with a goal from captain of the night Wayne Rooney; the striker's head met a cross from Angel Di Maria to equalize.
But Welbeck handed Arsenal the lead for the second time as he beat De Gea to the ball just outside the 18-yard box and tapped into an empty net just after the hour mark.
Di Maria was later sent off after receiving two bookings in quick succession as he was first shown a yellow card for diving and then was sent off after grabbing at referee Michael Oliver's shoulder in protest with just under 15 minutes left.
Arsenal have drawn against Bradford or Reading in the last four and Wenger expect a tough game.
"Last year we played a tricky game at Wembley in the semi-final and you expect that again," the manager said after the game.