The Gunners have not been out of top-flight football since 1919, and in addition to all the league meetings, they have frequently gone head-to-head with the Reds in domestic cup competitions.
Factor in a Champions League semi-final and the odd FA Charity or Community Shield and the two clubs have contested 216 competitive meetings in total, with more epic encounters sure to come. Here, we assess some of the key moments...
Humble beginnings: It was all a bit different when the clubs first met on 13th October 1894. United, known then as Newton Heath, faced Woolwich Arsenal at the Bank Street ground in east Manchester, with honours even after a 3-3 draw.
Record breaker: Since that first meeting there have been some memorable tussles, but one that still burns bright is our incredible 8-2 win at Old Trafford in 2011, the record victory in the history of the fixture.
The history man: Ryan Giggs has more reasons than most to look back on United v Arsenal meetings with pride. The veteran has featured in this fixture 49 times, a record that like others set by the Welshman will stand for a very long time to come. Of all of these games, the most memorable must be the FA Cup semi-final replay win at Villa Park (again) in 1999, where his stunning solo run and goal clinched a place in the final and kept the Treble dream on track.