It might be five years since they last faced off, but Jose Mouriho has never lost to a side coached by Unai Emery.
While their teams and indeed fortunes have changed significantly since then, Mourinho will be determined to continue his fine record against the Spaniard and history suggests the Red Devils can defy form to upset a red-hot Gunners side.
Unbeaten in their last 11 home Premier League games against Arsenal, United will be hoping Old Trafford can remain an unhappy hunting ground for their opponents on Thursday morning.
With the Gunners struggling to find success at the Red Devils fortress, they've also struggled in front of goal there - only scoring more than once in three of their last 39 league games at the venue.
Add to that equation the fact Arsenal lost both of their league games against Manchester United last season, plus a poor mid-week record which has seen them lose their last three Premier League games, and Mourinho will be hoping history remains on his side during a difficult period for the club.
The Red Devils have been struggling this season and after only just salvaging a 2-2 draw with Southampton last time out sit seventh on the table - eight points shy of the Gunners in fourth.
With Mourinho's time in Manchester marching towards an unhappy end, Emery has started life with a bang at Arsenal and claimed North London derby bragging rights with a 4-2 win over Tottenham on Monday.
The Gunners haven't lost in all competitions since a 2-0 defeat to Manchester City in August and have scored the second most goals this season in the league.
Arsenal's strong return in front of goal owes a lot to the competition's current top scorer, Pierre-Emerick Aubameyang, who has scored with each of his last 10 shots on target in the Premier League for the Gunners.
With United already leaking 23 goals across 14 games this campaign, something that took 30 matches last season, Mourinho will have his work cut out to keep Aubameyang quiet and in turn continue his fine record against a manager on the rise.