The Frenchman has never trumped Mourinho in 13 competitive games since they first clashed in 2004 and he has often been the loser off the pitch as well, with Mourinho taunting him about Arsenal's lack of title success over the past decade.
But Arsenal have a good opportunity to register their first Premier League win at Old Trafford since 2006 when they face a United team that could be without six players, including their first-choice defence.
Striker Zlatan Ibrahimovic is suspended and centre halves Eric Bailly and Chris Smalling are injured along with right back Antonio Valencia who is recovering from surgery on a broken arm.
There are also doubts about midfielder Marouane Fellaini and full back Luke Shaw as Mourinho grapples with the most serious injury crisis of his time at United.
Ibrahimovic's absence will give Marcus Rashford the chance to move to his natural position as central striker for the first of four straight United home games in all competitions.
The Old Trafford faithful will be looking for signs that Mourinho is making progress despite a disappointing start to his reign which has left them sixth in the table, six points behind fourth-placed Arsenal and eight adrift of leaders Liverpool.
Wenger's main injury doubt cleared up on Tuesday when forward Alexis Sanchez, whom he had urged to miss Chile's World Cup qualifier with Uruguay after tweaking a hamstring, showed no ill-effects after scoring twice in a 3-1 comeback win.
For once, Arsenal, who had 11 other players on full international duty last week, will be confident of winning on a ground where Wenger has often emerged an angry second best, most notably in 2011 when they were humiliated 8-2.
Liverpool travel to Southampton with a major doubt over their former Saints midfielder Adam Lallana, who suffered a groin injury after scoring a penalty for England in their 2-2 friendly draw with Spain on Tuesday.
However, such are coach Juergen Klopp's attacking options, with Daniel Sturridge and Divock Origi pushing for selection, that he will be confident of extending a run that has brought 14 goals in four games.
Former winger Steve Heighway became the latest Liverpool great to praise Klopp this week, saying the club's late manager Bill Shankly would have approved of the ethics Klopp is instilling at Anfield.
By that he meant how the team is playing, the desire for success and the way talent is being developed by the charismatic German.
Chelsea and Manchester City are also flourishing under new management with Antonio Conte's second-placed side at Middlesbrough on Sunday, 24 hours after Pep Guardiola's City, who are third, bid to make up ground at Crystal Palace.
Original source: Wenger looking to put one over Mourinho