The two sides regularly battled it out for some of English football's biggest prizes during the first two decades of the Premier League era, with many of these clashes going down as all-time classics.
And while fixtures between the pair were once filled with confrontation and individual feuds, the rivalry has become a much less intense affair in recent years.
Following the departure of Sir Alex Ferguson in 2013, the Red Devils have struggled to mount a serious title challenge, while the Gunners have only re-entered the title conversation in the past two seasons.
And as the two sides prepare to face off for the first time this season at the Emirates Stadium on Wednesday night, the recent lack of competitive edge to the rivalry could not be clearer.
With Arsenal finishing as runners-up to champions Manchester City in each of the last two seasons, while United have come in at third and eighth respectively, Mikel Arteta's group have established a real dominance over their once great rivals during this time.
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The Gunners have won their last three Premier League encounters against the Red Devils and head into the clash with a chance to record a league first.
Arsenal have never been victorious in four consecutive league fixtures against the 20-time English champions.
And with the upcoming fixture taking place on home soil, Arteta's side can further assert their current superiority over their old enemy by continuing their pursuit of another record.
The Gunners have recorded a hat-trick of league victories against United at the Emirates in as many seasons, winning 3-1, 3-2 and 3-1 again.
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This means the north Londoners are now chasing their own club best, with the last team to score three or more goals in consecutive home league games against the Red Devils being Arsenal themselves.
Between 1970 and 1978, the Gunners managed to achieve this feat in a staggering seven games in a row.
And Arsenal won't just be targeting team records tomorrow night.
Bukayo Saka is looking to close in on Thierry Henry's impressive record against United, who leads the way in Gunners goal involvements in this fixture.
The Frenchman scored eight goals and registered four assists during his eight years in London, while the English winger has currently contributed to five goals here - three goals and two assists.
Should Saka provide the key pass for one of his teammates in the clash, he will also draw closer to matching another record of Henry's.
The Arsenal legend recorded a Premier League best of 20 assists in the 2002/03 season, a figure which the 23-year-old will surely be targeting, with his current season tally standing at 10 already.
Last season's runners-up will certainly fancy their chances of continuing their recent run of form against the Old Trafford outfit.
Arsenal currently sit second in the league, nine points behind leaders Liverpool, and are six points ahead of United, who are languishing in ninth.
The North West giants are also navigating period of transition, with the upcoming Emirates encounter only new head coach Amorim's fourth game in charge of the club.
Amorim is without the suspended Kobbie Mainoo and Lisandro Martinez, while defender Luke Shaw has suffered a fresh injury setback, but their recent record could weight Man United down even more.
The current state of affairs is a far cry from the two sides' rivalry back in the 1990s and 2000s, which saw Arsenal and United the only clubs to win the Premier League between 1997 and 2004.
During this time, Ferguson's side lifted the league title five times to Arsene Wenger's group's three, whilst also collecting five FA Cups between them in the same period.