Roy Hodgson's men are yet to pick up a point or score a goal in their six league outings so far this season and face a team that has won five out of six and conceded only twice.
Opta outlined just how poor a start to the season it has been for Palace:
Here is how you can watch the game:
Date: Saturday, Sept. 30
Time: 3 p.m. BST/10 a.m. ET
TV Info: NBCSN and NBC Universo (U.S. only)
Live Stream: NBC Sports Live Extra (U.S. only)
Manchester United have injury problems, particularly in midfield. They are still without Paul Pogba, while Michael Carrick will miss the game and Phil Jones is a doubt, per Samuel Luckhurst at the Manchester Evening News:
Meanwhile Anthony Martial was substituted against CSKA Moscow and appeared to have a problem, per Luckhurst:
WhoScored.com highlighted just how important Benteke is to the Eagles:
With Connor Wickham also still out, Palace are left short of options up front, although they could use winger Bakary Sako as a striker.
Wilfried Zaha also remains sidelined, although he is closing in on a return to first-team action after returning to training, per Mark Ritson of the Croydon Advertiser.
Palace's hopes of picking up their first points of the season at Old Trafford look slim with United having won all three home league games without conceding a goal.
The Eagles may be hoping fatigue plays a part with the hosts having played in Russia in midweek.
However, Mourinho has spent heavily since taking over in May 2016, and his squad should be strong enough to cope with the demands of both domestic and European football.
The main threat for United will again be Romelu Lukaku who already has six Premier League goals and will be relishing taking on a side that has conceded 13 in six games.
The Belgian is in top form and has certainly done enough to impress football writer Liam Canning:
Palace reportedly prepared for the game with a friendly against National League side Bromley, a match arranged to help "rebuild shattered confidence," per John Cross at the Mirror.
Hodgson certainly needs to do something as he has been unable to turn results around since replacing Frank de Boer as manager, as noted by Match of the Day host Gary Lineker:
Any kind of result at Old Trafford would be a massive boost for Palace, particularly with Chelsea up next, but current form and home advantage suggests a comfortable United win is the most likely outcome.