The Red Devils go into the match sitting eighth in the table, while Palace are only outside the relegation zone on goal difference courtesy of a seven-match winless run.
Jose Mourinho's side were always going to be underdogs away to the Premier League champions and leaders, but their local rivals were so comfortable in their victory that it was another stark reminder of how far off the pace United are at the moment.
Nineteen points separated the two sides at the end of last season, and the Red Devils have already fallen 12 points adrift of Pep Guardiola's men after just 12 games of the current campaign.
Any ambitions of a title challenge appear to have expired already, then, but United can ill afford any more slip-ups if they still harbour hopes of qualifying for next season's Champions League.
Nights like the away win over Juventus - arguably United's best result of the post-Sir Alex Ferguson era - will only be possible if they finish in the top four this season, but they already find themselves seven points off fourth-placed Tottenham Hotspur.
Defeat to Crystal Palace in what is United's first home game in almost a month could see that gap grow to double figures, but there were signs of Mourinho's men beginning to build some momentum prior to their derby defeat.
Three successive 2-1 wins included two from behind, while their recent improvement has also featured a rousing comeback triumph over Newcastle United - a result which may well have saved Mourinho's job.
While such comebacks have squashed the suggestion that the players are no longer willing to fight for their beleaguered boss, United simply have to produce an answer to the question of why they are starting matches so slowly.
Remarkably, Mourinho's side have trailed for 395 minutes in the Premier League this season; only the three clubs in the relegation zone have been behind for longer.
It is an embarrassing statistic which goes a long way to explaining why United find themselves in such dire straits, sitting eighth in the table and as close to the relegation zone as they are to the league leaders.
The Red Devils will be glad to be back at Old Trafford for the first time since October 28, but they have won just two of their last seven outings in front of their own fans and are without back-to-back victories on home turf so far this season.
United are also without a home clean sheet in the Premier League this season and overall have already shipped 21 goals in 2018-19 - the fifth-worst record in the league and a tally it took them until matchday 29 and March 5 to reach last term.
Should they fail to keep a clean sheet again on Saturday then it would be the club's joint-longest run without one in the Premier League, equalling the nine-game streak from 1999.
Recent Premier League form: LWDWWL
Recent form (all competitions): DLWWWL
Roy Hodgson will not be hitting the panic button for Palace just yet, but he will know that his side are in growing need of a positive result ahead of their trip to Old Trafford.
The team's current struggles should be kept in the context of last season, when they sat bottom of the table at this stage of the campaign, but they were just three points worse off then despite having lost their opening seven games of the season without scoring a single goal.
Palace got off to a much quicker start this time around with victory on the opening day, but that is one of only two wins they have managed during the current campaign, both of which have come against teams who now sit in the relegation zone.
The Eagles arrive at Old Trafford without a win in seven league outings stretching back to mid-September, since when they have picked up just two points from the 21 on offer.
Hodgson can justifiably argue that his side have deserved more from those games, and he may well take confidence from the fact that his side's best result from their last six outings came against Arsenal, but he knows that ultimately it is points on the board which matter.
The silver lining to the current cloud Palace find themselves under is that Saturday marks the final game of a torrid run which will have seen them face four of last season's top six in succession.
Hopes of ending their current poor run of form this weekend may not be particularly high, though, considering Palace have a dreadful record at Old Trafford and have lost four of their five away games so far this term.
Indeed, home and away only basement club Fulham have lost more matches than Palace so far in 2018-19, so it is no surprise that only goal difference is keeping them outside of the relegation zone as things stand.
It is the Eagles' defensive record which is mostly to thank for that; only Newcastle United have conceded fewer inside the bottom nine, whereas only Huddersfield Town have scored fewer in the entire league so far.
United's own defensive woes will act as encouragement for Palace, then, but Hodgson may have one eye on an upcoming run of games against fellow bottom-half dwellers Burnley, Brighton & Hove Albion and West Ham United as a better chance to turn the team's fortunes around.
Recent Premier League form: LLLDLL
Recent form (all competitions): LLDLLL
United will be without the suspended Luke Shaw after he picked up his fifth yellow card of the season in the derby last time out.
Ashley Young is likely to switch over to left-back as a result, meaning that Mourinho must decide between recalling the out-of-favour Antonio Valencia or handing a league debut to Diogo Dalot at right-back.
There are bigger injury problems further up the pitch, with Paul Pogba having missed both the derby and the international break with a thigh problem.
Anthony Martial, Marcus Rashford, Marouane Fellaini and Romelu Lukaku all returned from international duty carrying knocks too, although all four - in addition to Pogba - are in contention to feature.
Martial in particular will be hoping to start in order to continue his recent fine form, and a goal on Saturday would see him join Eric Cantona, Ruud van Nistelrooy and Cristiano Ronaldo as the only players to score in six successive Premier League games for United.
Palace, meanwhile, are boosted by the return of former United attacker Wilfried Zaha, who had been struggling with a thigh injury but has been passed fit for this match.
Man Utd possible starting lineup:
De Gea; Dalot, Smalling, Lindelof, Young; Herrera, Matic, Pogba; Lingard, Rashford, Martial
Crystal Palace possible starting lineup:
Hennessey; Wan-Bissaka, Sakho, Tomkins, Van Aanholt; McArthur, Kouyate, Milivojevic, Schlupp; Townsend, Zaha
Head To Head
Palace have never beaten United in their 18 past Premier League meetings, losing 15 of those in what is the longest run without ever winning against a certain opponent in the competition's history.
Indeed, it is 20 league games since Palace last beat United, losing 17 and drawing three since a 3-0 triumph in May 1991.
The Eagles' record at Old Trafford is even worse; United have won the last 11 league meetings here, with Palace failing to score in 10 of those stretching back to a 2-1 triumph in December 1989.
We say: Man Utd 1-0 Crystal Palace
Manchester United have been far from convincing at home this season, but Palace are in poor form at the moment and have a miserable record at Old Trafford too. The Eagles have not made it as easy for opponents as their recent results suggest, but they could be in line for another defeat this weekend.