The shocking transfer of the Dutch striker has caused both sides to face completely different fortunes so far in this young campaign.
Heading into this highly billed fixture, United sit in second place with 21 points, just one point behind Chelsea. This is the same Chelsea side that United defeated 3-2 last weekend at Stamford Bridge.
Arsenal are currently sitting in sixth place, seven points behind Chelsea. The Gunners have put forward some strong performances, like their 2-0 win at Anfield in September. Yet poor showings against sides like Norwich City have come to appropriately represent this season's Arsenal side.
The early season success achieved by Manchester United so far has put them in a strong position to win their 20th league title.
United's defense has been porous at times, but van Persie has been the best footballer in England, already scoring nine combined goals in both the Champions League and the Premier League.
Arsenal have gone down a different road than United.
After van Persie's play got the Gunners an automatic berth in this seasons' Champions League with a third place finish, Arsenal appear lucky to get a Europa League spot, considering their weak start so far.
Last year, Arsenal also had a weak start, but there are no players on this year's squad that are capable of producing the brilliance similar to that exhibited by van Persie last year.
Those two starts will coincide at Old Trafford in a matchup in which United are deserving favorites.
Looking at recent history in Premier League play only further backs this point:
Arsenal 1, Manchester United 2 (Jan. 22, 2012)
Manchester United 8, Arsenal 2 (Aug. 28, 2011)
Arsenal 1, Manchester United 0 (May 1, 2011)
Manchester United 1, Arsenal 0 (Dec. 13, 2010)
Arsenal 1, Manchester United 3 (Jan. 31, 2010)
United have dominated recent matchups between the two sides. Since the start of 2009, United lost to Arsenal just once, which came at the end of the 2010-11 campaign.
There have been 10 matches between the two sides during this time, with United holding an 8-1-1 edge. The draw that the Red Devils had with Arsenal in 2009 secured United their then record-tying 18th league title.
Heading into this crucial league fixture, here are the final five matches that these sides have partaken in.
Chelsea 5, Manchester United 4 (Oct. 31, Capital One Cup)
Chelsea 2, Manchester United 3 (Oct. 28, Premier League)
Manchester United 3, Braga 2 (Oct. 23, Champions League)
Manchester United 4, Stoke City 2 (Oct. 20, Premier League)
Newcastle United 0, Manchester United 3 (Oct. 7, Premier League)
Reading 5, Arsenal 7 (Oct. 30, Capital One Cup)
Arsenal 1, Queens Park Rangers 0 (Oct. 27, Premier League)
Arsenal 0, Schalke 04 2 (Oct. 24, Champions League)
Norwich City 1, Arsenal 0 (Oct. 20, Premier League)
West Ham United 1, Arsenal 3 (Oct. 6, Premier League)
Chris Smalling is still recovering from a broken metatarsal, but will not be ready to return this week. Phil Jones (knee) will also miss this match, though he should return within the next two weeks.
Nemanja Vidic (knee) and midfielder Shinji Kagawa (knee) remain sidelined. It was announced yesterday that Vidic will probably be out until Christmas.
Gervinho (ankle), Kieran Gibbs (thigh), Wojciech Szczesny (ankle), Abou Diaby (thigh) and Tomas Rosicky (hamstring) will all miss this match as they continue their rehabilitation.
Alex Oxlade-Chamberlain (hip) is questionable and will face a fitness test before the start of the match. Theo Walcott might not play after playing 120 minutes in the Gunners, thrilling 7-5 win at Reading in the middle of the week.
The start to this season has been disparaging defensively. United have conceded the first goal in eight of the 14 matches that they have played to date.
This previous back means that United will need to outscore Arsenal in this fixture. Considering the circumstances, none other than Robin van Persie is the key player for the Red Devils in this fixture.
In five of the six matches that the Dutch striker has scored in this season, United conceded the first goal.
United have also not lost to date when he scores.
After a 17-month absence, Jack Wilshire finally made his long-awaited return to the Gunners during last weekend's win against QPR.
With plenty of injuries plaguing Arsenal's squad at the moment, they will need a strong performance from their young star at Old Trafford.
Considering that Arsenal have scored just 10 goals in 20 Premier League visits to Old Trafford, with their only multi-goal effort coming in last season's historic 8-2 loss, Wilshire will need to put in his best work for Arsenal to come out on top.
There are plenty of interesting stats that will side with United in this matchup.
Wayne Rooney has achieved tremendous success against Arsenal. Rooney’s 10 goals against Arsenal is tied for the highest by an EPL player against the Gunners, alongside Robbie Fowler.
Rooney's 10 goals are tied for the most he has scored against any Premier League opponent.
United have also scored in their last 53 league matches at the Theatre of Dreams, a Premier League record.
Arsenal have failed to win at Old Trafford since 2006 when Emmanuel Adebayor scored a late winner.
There is too much going against Arsenal heading into this fixture. They are without several of their top players and Man United's football is at a high level.
Even with a weak defense, it is unlikely that United would lose this fixture. Through 12 matches in both the Champions League and the Premier League, United have not had one draw.
That streak will extend past 13 matches, for United will secure another important win.
Manchester United 3, Arsenal 1