For the Red Devils, who are currently sixth in the Premier League on 18 points, victory would see them temporarily close the gap on league-leaders Liverpool to five.
As for Arsenal, they're in the thick of an exciting title race and can fire themselves to the top of the table with all three points.
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Recent form dictates the away side should emerge victorious - but history tells us otherwise.
Back in February, with Arsenal flying high and gunning for the title, Marcus Rashford's brace secured United a memorable home win over their rivals.
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But four months previously, at the Emirates Stadium, Arsenal ran riot and put three past David de Gea in a comfortable 3-0 victory.
Predicting Saturday's result is simply impossible.
The mind games have well and truly begun in the build-up, with United's Twitter account using a #MondayMotivation post to embarrass Arsenal (see below).
United refer to four previous encounters in their post, with 2011's 8-2 mauling at Old Trafford and the 6-1 win 10 years previously undoubtedly the most humiliating for Arsenal.
Injuries have plagued both sides ahead of the clash, although Wenger is reportedly the more worried with several key players at risk of missing out.
The Frenchman has asked for Laurent Koscielny to miss France's game against Ivory Coast on Tuesday night, while Santi Cazorla has suffered another injury blow and Alexis Sanchez continues to play for Chile despite nursing a hamstring problem.
"France plays a friendly with Ivory Coast in the second game on Tuesday night. I can't see the purpose of Koscielny playing the second game," Wenger said.
And on Sanchez, he added: "I believe that with a hamstring injury, we have to get access for our medical staff to the MRI scan to see what grade it is, how bad it is and make absolutely sure they don't make any suicidal decision that could harm his future for two or three months.
"That is absolutely important. It's a grey area between the national team and the club team and of course they look at their own results, which I can understand, but we have to preserve the health of Alexis Sanchez.
"He always wants to play and that's where it is a more sensitive case because he's always ready to play even when injured."