Ole Gunnar Solskjaer's side get their season underway this afternoon Palace making the trip north looking to cause another shock at Old Trafford.
Jordan Ayew's goal sealed a memorable win for Roy Hodgson's side last season - can they do it again?
Follow all the action with Standard Sport's LIVE blog!
- GOAL! Zaha scores third for Palace
- GOAL! Van de Beek pulls one back on his debut
- GOAL! Zaha scores penalty after retake
- GOAL! Townsend puts Palace ahead after seven minutes
- Manchester United starting XI: Greenwood on the bench
- Crystal Palace starting XI: Eze and Batshuayi among subs
Date, time and venue
Manchester United vs Crystal Palace is scheduled for a 5:30pm BST kick-off on Saturday, September 19.
This match will be played behind closed doors at Old Trafford with no fans due to be present due to government guidelines regarding coronavirus.
How to watch
TV channel: The match will be televised on Sky Sports Main Event and Sky Sports Premier League, with coverage starting from 5pm.
Live stream: Sky Sports subscribers will be able to stream the match online via the website and SkyGo app.
Paul Pogba is the main doubt for United. The World Cup winner contracted coronavirus this summer and as such missed a number of United's preseason training sessions.
Solskjaer is hopeful the midfielder will be ready, but Pogba could well be a bench option - and that could mean a full debut for summer signing Van de Beek.
The only other absences for United are Axel Tuanzebe and Phil Jones, meaning Teden Mengi may be among the substitutes.
As for Palace, Hodgson remains without a number of centre-backs but has plenty of options going forward.
Both Eberechi Eze and Michy Batshuayi were handed starts in Tuesday's 0-0 draw with Bournemouth in the Carabao Cup, where the Eagles were knocked out on penalties.
Eze is yet to start a League game for Palace, while Batshayi spent his first league game back at the club watching the win over Southampton from the bench.
The Belgian could well be thrown in to lead the line at Manchester United on Saturday, though Hodgson may feel it is too soon for Eze given how much work he will have to do on the ball.
Given the injuries, Hodgson's back four picks itself while captain Luka Milivojevic could well return to start in midfield having come off the bench against the Saints.
Prediction: Man United 2-1 Crystal Palace
Given that Palace won here last season and also started the new campaign with a promising 1-0 win over Southampton, they will have no fears facing this United side.
The hosts will be under pressure to hit the ground running and though there may be a few cobwebs, you'd still expect United to get the win - but it could be tight.