The Red Devils begin their campaign a week later than most teams due to their involvement in the latter stages of the Europa League last term, but have still had little more than a month off in a quick turnaround between seasons.
United ended 2019-20 with a 14-game unbeaten run in the Premier League and will look to build on their third-placed finish last term, but they face a Palace side that won on the opening day and picked up their first ever Premier League win over United in the corresponding fixture last season.
Here, Sports Mole looks at how Ole Gunnar Solskjaer could set his side up for Saturday's showdown.
Solskjaer has only had his full squad together for a week or so in the build-up to this match so, while their injury list does not look too extensive, many players may be short of full match fitness for this game.
Paul Pogba is one of those after his preparations were disrupted by a positive coronavirus test, something which he has now fully recovered from but which did delay his return to training.
Whether Pogba is fit or not, new signing Donny van de Beek will be pushing for his debut, having featured in the club's solitary pre-season friendly against Aston Villa.
As many as seven first-team players did not take part in that 1-0 defeat, though, including goalkeeper David de Gea, whose status as the club's number one has come under threat from the returning Dean Henderson.
Solskjaer is expected to keep faith with De Gea at the start of this season, but Henderson has insisted that he is not at the club to be a back-up and the recent five-year contract he signed suggests that he will play a part in United's immediate future.
Other players to have missed the friendly at Villa Park include Victor Lindelof, Bruno Fernandes, Anthony Martial and former Palace defender Aaron Wan-Bissaka, but all of them should be in contention this weekend.
Mason Greenwood's off-field actions during his maiden international call-up could cost him a starting spot in this season opener, but Harry Maguire, who also hit the headlines for the wrong reasons this summer, will start after retaining the captain's armband.
Axel Tuanzebe is United's only confirmed absentee, while Phil Jones is still struggling with a knee problem.