The battles between Arsenal and United defined the opening decade or so of Wenger's 22-year reign at the club, while his bitter rivalry with Mourinho has also been one of the abiding memories of his time in North London.
There is more than just bragging rights on the line this weekend, though, as Arsenal need a win to keep their slim top-four hopes alive - something which seems more important than ever after they gave up the advantage in the first leg of their Europa League semi-final on Thursday.
Here, Sports Mole looks at how the Gunners could line up for the trip to Manchester.
Out: Mohamed Elneny (ankle), Santi Cazorla (Achilles)
Doubt: Henrikh Mkhitaryan (knee)
Wenger has a difficult balance to strike heading into this match, with neither possible route into next season's Champions League looking particularly likely at this stage.
The Europa League route is still in their hands, though, while the same is not true of the Premier League, so Arsenal could rest a number of key players this weekend in order to keep them fresh for the return leg away to Atletico Madrid on Thursday.
Pierre-Emerick Aubameyang is expected to lead the line as he is ineligible to play in the Europa League, while Danny Welbeck and Alex Iwobi could join him in the front three - although Welbeck may be one of the players rested.
Henrikh Mkhitaryan is nearing full fitness but will likely be held back ahead of Thursday, but Petr Cech is expected to return to the starting lineup having missed his side's last two games.
The likes of Calum Chambers, Rob Holding and 18-year-old Joseph Willock could be given rare starts, and fellow youngsters Ashley Maitland-Niles, Reiss Nelson and Eddie Nketiah will also be hopeful of featuring.
The injury-plagued Santi Cazorla is back in training, meanwhile, but he will not return until next season following a lengthy spell on the sidelines.