The rivalry was at its peak at the turn of the millennium when the two sides were challenging only each other in pursuit of league glory.
However, the arrival of Chelsea and Manchester City as genuine footballing superpowers has upset the balance somewhat, and Arsenal at least find themselves out of the reckoning in the race for the title.
But, when the Gunners and United meet it is always an intriguing encounter, as the two greatest managers in Barclays Premier League history go head-to-head.
In preparation of the clash between the pair at the Emirates Stadium on Sunday, GMF takes a look back at some of the more memorable encounters between the two sides that have taken place in north London...
Arsenal 3-2 Manchester United, November 9 1997
United were chasing a third successive league crown when they travelled to Highbury during Arsene Wenger's first full season at Arsenal.
Nicolas Anelka gave the Gunners the lead after only seven minutes, and their advantage was doubled before half-time thanks to a memorable strike from Patrick Vieira.
However, Teddy Sheringham netted twice prior to the break to restore parity, before David Platt headed in at the near post in the final minutes of the 90.
Arsenal went on to win the double.
Arsenal 1-2 Manchester United, August 22 1999
Two goals from Roy Keane gave United a vital victory against Arsenal and ended the Gunners' unbeaten 20 month record at Highbury.
Arsenal led 1-0 at the break thanks to a strike from Freddie Ljungberg, who finished off a free-flowing move led by Nwankwo Kanu.
Keane, though, combined with Andy Cole to level proceedings after half-time, before beating Alex Manninger again with only two minutes remaining.
United ended the season by lifting their 13th league title.
Arsenal 2-2 Manchester United, April 17 2003
Billed as a potential title decider, this enthralling deadlock left United three points clear of Arsenal heading towards the final month of the season.
Sir Alex Ferguson's side ran out eventual winners in the race for the league crown, but were unable to get the better of the Gunners during this encounter.
Ruud van Nistelrooy put the visitors ahead after 23 minutes and were given a further boost when Patrick Vieira limped off with just over half an hour gone.
However, Thierry Henry levelled proceedings five minutes after the break, before putting the Gunners in front shortly after the hour mark.
But their lead lasted only seconds as United restored parity courtesy of a header from Ryan Giggs.
More drama was to unfold in the closing stages as Sol Campbell received his second red card of the season after elbowing Ole Gunnar Solskjaer.
Arsenal 2-4 Manchester United, February 1 2005
Arsenal and United were both trailing Jose Mourinho's Chelsea when they met in February, and the Blues went on to win the league in May.
However, these two great foes played out a thrilling encounter at Highbury, in which United came from behind to win in convincing fashion.
Patrick Vieira and Dennis Bergkamp scored either side of a strike from Ryan Giggs to ensure Arsenal were leading after 45 minutes.
However, Cristiano Ronaldo made the score 2-2 nine minutes after half-time, before giving United the lead four minutes later.
John O'Shea then completed the scoring in the closing stages when he beat Manuel Almunia with an audacious chip.
Arsenal 2-1 Manchester United, January 21 2007
The first meeting between Arsenal and United and the newly built Emirates Stadium was also the 200th encounter between the two clubs.
And few of the previous 199 could have matched the drama of the final stages of this fixture as Arsenal stole three points with seconds left on the clock.
United had led thanks to a goal from Wayne Rooney on the hour mark, but were to crumble to defeat in the closing stages.
First, with seven minutes remaining, Robin van Persie equalised with his sixth goal for the Gunners in seven games.
However, such was the Dutchman's excitement, he broke a bone in his foot while celebrating after sliding home a precise pass from Tomas Rosicky.
Arsenal, though, were not finished and Thierry Henry thumped home a header from an Emmanuel Eboue cross to send the Gunners faithful into raptures.