They first met on 13 October 1894 as Woolwich Arsenal v Newton Heath, and one of England's greatest rivalries was born.
Today, they are better known as Arsenal and Manchester United, and they meet for the 220th time on Monday in The FA Cup Sixth Round Proper.
From Wenger v Ferguson and Keane v Vieira, to last-minute FA Cup Semi-Final wins and Premier League glory in the other's backyard – the fixture has thrown up some classic moments over the years.
We look back at five of the most memorable...
Have a look at some of the classic FA Cup ties between the two clubs
Manchester United 2-1 Arsenal (aet), FA Cup Semi-Final Replay, 14 April 1999
It was the last FA Cup Semi-Final replay ever to be played and it was arguably one of the greatest games in the competition's history.
After they drew the first encounter 0-0, the pair met again three days later. David Beckham put Manchester United ahead with a stunning curling effort on 17 minutes.
Dennis Bergkamp's deflected shot then drew the Gunners level – and after a disallowed Arsenal goal, a red card for Roy Keane and a last-minute penalty save from Peter Schmeichel, up stepped Ryan Giggs.
The Welsh winger pounced on a loose Vieira pass inside his own half. He proceeded to beat five Arsenal players and fire the ball past David Seaman, United into The Final and himself into FA Cup folklore.
Manchester United 0-1 Arsenal, Premier League, 8 May 2002
Sylvain Wiltord ensured his name would be forever remembered among the Arsenal faithful as he scored the only goal in their 1-0 victory at Old Trafford in 2002.
It was not just any old win, for the three points ensured Arsene Wenger's side also left Manchester as Premier League champions.
A draw would have been enough to end Manchester United's three-year reign as champions, but the former France international struck just before the hour mark to send the 3,000 travelling fans into jubilation – and gave them an evening they still remind the United fans about every time the pair meet.
Arsenal 3-2 Manchester United, FA Cup Final, 12 May 1979
Widely regarded as one of the greatest Finals in FA Cup history, Arsenal and Manchester United played out a five-goal thriller in front of almost 100,000 fans at Wembley back in 1979.
Despite its ‘classic’ status, the Final was somewhat unremarkable for 85 minutes after Arsenal raced into a two-goal lead thanks to goals from Brian Talbot and Frank Stapleton.
However, strikes from Gordon McQueen and Sammy Mcllroy on 86 and 88 minutes respectively hauled Dave Sexton’s side back into the tie.
It looked to be heading toward extra time, until Alan Sunderland scored a dramatic last-minute winner for Arsenal – in what would go down in history as the "Five-minute Final".
Manchester United 8-2 Arsenal, Premier League, 28 August 2011
The highest scoring of the pair's 219 meetings to date came four years ago, when Manchester United bulldozed an injury-plagued Arsenal side 8-2 at Old Trafford.
Wayne Rooney grabbed a hat-trick, Ashley Young scored two fine solo goals and Danny Welbeck, Ji Sung Park and Nani all chipped in as Sir Alex Ferguson's side inflicted total humiliation on their hapless guests.
Robin van Persie and Theo Walcott did pull goals back for Gunners, but by then the damage was done – and the heaviest defeat in Arsene Wenger's 19-year tenure at Arsenal was complete.
Arsenal 0-0 Manchester United (Arsenal won 5-4 on penalties), FA Cup Final, 21 May 2005
What the 2005 FA Cup Final lacked in drama during the 120 minutes of action, it was more than made up for in the ten penalty kicks that followed.
Sir Alex Ferguson's side – who had won both league meetings with Arsenal that season – dominated the game, controlled possession and had the best of the clear-cut chances.
However, even with a team containing the attacking prowess of Cristiano Ronaldo, Ruud van Nistelrooy and Wayne Rooney they were unable to beat Jens Lehmann in the Arsenal goal.
The game went to penalties and Paul Scholes was the only player to miss, leaving Patrick Vieira to take the winning spot-kick.
It also proved to be his last action in an Arsenal shirt, and the last time the Gunners tasted silverware of any kind for nine long years, until they lifted The FA Cup once again in 2014.
Manchester United take on Arsenal in The FA Cup Sixth Round on Monday 9 March.
The game gets under way at 7.45pm and it is live on BBC One.