It is a fixture which has lost some of its edge in recent years due to the waning fortunes of both clubs, although there remains plenty of animosity between the two sides whenever they meet.
Each will be looking to get one over on the other this weekend, and as part of the build-up to Saturday's showdown Sports Mole has selected the strongest combined XI from the two squads in a 3-4-3 formation, using only players who are available this weekend.
GK: David de Gea
Petr Cech was certainly the best goalkeeper in the Premier League at one stage, but that crown has now been passed to David de Gea and the Spaniard beats Cech to the gloves in this team as a result.
Even with the two goals they conceded against Watford in midweek, United boast the best defensive record in the Premier League this season with De Gea having kept a league-high nine clean sheets from 14 games.
The 27-year-old regularly pulls off remarkable saves to keep the opposition at bay, and without him United would have struggled even more in recent years.
Long regarded as Arsenal's best defender, Laurent Koscielny has again performed to a high standard on a regular basis this season.
The France international has started 11 of Arsenal's 14 Premier League matches in the current campaign, helping the club to three clean sheets in a row heading into Saturday's match against United.
Arsenal's defence has been questioned at times this season, but Koscielny's own performances have barely wavered and he narrowly earns a place above Nacho Monreal in this side.
CB: Shkodran Mustafi
With Phil Jones expected to miss the weekend match through injury, Shkodran Mustafi earns his place at the heart of the back three in this team.
The Germany international has only made eight Premier League appearances so far this season, but he has arguably been Arsenal's most impressive defender in that time.
Mustafi leads the way for the average number of both tackles and clearances per game for the Gunners this season, in addition to scoring one vital goal in the North London derby against Tottenham Hotspur.
CB: Eric Bailly
Eric Bailly has missed United's last four games with a groin strain, but the Ivorian could be in line to return this weekend and that is enough for him to earn a place in this team.
No player to have featured regularly for United this season has averaged more clearances per game than Bailly, while he is also one of the leaders when it comes to blocks per match amongst the Red Devils squad.
RWB: Antonio Valencia
Having learned his trade as a winger before being moved into full-back for a stint, Antonio Valencia now seems to have discovered his best position as a right wing-back.
The 32-year-old has been an ever-present for United in the Premier League so far this season, helping the team to boast the best defensive record in the league while also helping himself to one goal at the other end.
Competition for a place in this team comes from Hector Bellerin, but the Spaniard has not been at his best for a while now despite being one of only two outfield Arsenal players to have played every minute of the season so far.
CM: Paul Pogba
Paul Pogba's value to Manchester United was perhaps best demonstrated by his time out of the team, and his return brought with it an immediate upturn in form from the Red Devils.
The £89m man has directly contributed to six goals already this season despite being limited to just seven Premier League appearances, scoring three and creating three more for the Red Devils.
Arsenal have Granit Xhaka as competition for a place in the heart of the midfield, but Pogba is capable of performing a holding role and getting forward, which makes him an easy choice above the Switzerland international.
CM: Aaron Ramsey
Perhaps an attacking choice to partner Pogba at the heart of the midfield, but both players are disciplined and clever enough to know that when one goes forward, the other needs to stay in position.
Ramsey, like Pogba, is capable of doing both jobs. The Welshman has directly contributed to eight goals in the Premier League already this season, scoring three himself and setting a further five up for his teammates.
Nemanja Matic would ordinarily partner Pogba in midfield in this side, but the Serbian limped off during the win over Watford at the weekend and is considered a major doubt for the weekend.
LWB: Sead Kolasinac
Ashley Young has made the left wing-back position his own for United, and his two goals against Watford in midweek certainly enhance his claim for a place in this side, but Sead Kolasinac gets the nod.
The Bosnian has quickly established himself as one of Arsenal's most important players since his summer arrival, scoring one goal and creating four more in his 13 Premier League appearances.
The battle between Kolasinac and Valencia on the flank is likely to be a key one on Saturday, with both aiming to pin their opposite number back into their own half.
RW: Alexis Sanchez
Despite not quite hitting his best form so far this season, Alexis Sanchez still has five goals and two assists across all competitions, including scoring in each of his last three Premier League outings.
Speculation continues to rage over the future of the Chilean, but he does at least now seem to be getting close to his own high level of expectation despite rumours of a January exit.
CF: Romelu Lukaku
Romelu Lukaku got off to a blistering start to his time at United, but he has very much gone off the boil in recent weeks with only one goal in his last 11 outings for the club.
Even so, the Belgian boasts an impressive tally of eight goals and four assists in the Premier League so far this season, while in all competitions his tally of goals scored sits at 11 from 20 appearances.
Alexandre Lacazette would usually provide stiff competition for a Lukaku in wasteful form, but the Frenchman looks set to be sidelined this weekend after being taken off at half time of the win over Huddersfield Town.
LW: Mesut Ozil
Another whose future has been an even bigger talking point than his form this season, Mesut Ozil showcased exactly what he can do during a dazzling five-minute spell against Huddersfield on Wednesday.
The German assisted two and scored one of his own as Arsenal took the game away from the Terriers in the blink of an eye, leaving Ozil with two goals and five assists for the season.
Anthony Martial and Marcus Rashford both run Ozil close for a place in the team, with Martial having taken his tally to eight goals in all competitions in midweek, but both narrowly miss out to the World Cup winner.