Mourinho has been paying tribute to Wenger since the Frenchman's announcement that he will step down at the end of the season, but the Portuguese will no doubt relish the chance to get the last laugh over the man he once labelled a specialist in failure.
The final chapter of the bitter rivalry could be a significant one too, with anything other than a win for Arsenal seeing a top-four finish officially ruled out, while United are looking to couple their FA Cup final place with their best Premier League finish since 2013.
Here, Sports Mole looks at how United could line up against the Gunners.
Mourinho could name an unchanged side to the one which beat Arsenal's North London rivals Tottenham Hotspur in the FA Cup semi-final last weekend, with Lingard and Valencia both expected to recover from knocks to feature.
The biggest decision for Mourinho to make could come in defence, where Bailly remains a doubt due to illness. Bailly has not played since the Manchester derby, but is likely to be restored to the team ahead of Phil Jones should he be fully fit.
There will be plenty of focus on Alexis Sanchez too, with the winger coming up against Arsenal for the first time since leaving the club in January, and Mourinho is expected to keep faith with him again despite growing calls for Anthony Martial or Marcus Rashford to be given a chance.