The Red Devils are 14 places and 30 points better off than their visitors in the Premier League table, but have found the Clarets an unlikely bogey team on home turf in recent years.
On first glance, a home tie against a Burnley side not quite clear of danger but with a comfortable cushion over the relegation zone looks like a kind fixture for Man United as they bid to mathematically secure a top-four spot.
However, the Clarets won the corresponding fixture last season and are unbeaten in their last four Premier League visits to Old Trafford, drawing the other three.
Sean Dyche's side find themselves in the unlikely position to become just the second team in Premier League history to avoid defeat in five consecutive away games against Man United, with Chelsea from 1994 to 1998 the only other team to have achieved that feat.
Indeed, the home side has failed to win any of the last nine meetings between these two clubs, and another win for Burnley would see them triumph in back-to-back away games against Man United for the first time since 1962.
The Red Devils have also not completed the league double over Burnley since 1975-76, so there is every reason for them to be wary of their visitors despite the gulf between the two sides in the table.
Even so, there is no doubt that the hosts will go into the game as firm favourites to come away with a fifth consecutive top-flight win - something they have not managed since winning their first six under Ole Gunnar Solskjaer.
Solskjaer got one over on his predecessor Jose Mourinho in their last league outing as Man United beat Tottenham Hotspur 3-1, further solidifying their place in the top four heading into the closing weeks of the season.
The ensuing war of words between Solskjaer and Mourinho - which was continued by Paul Pogba's scathing criticism of his former manager in the week - may have stolen many of the headlines since, but Solskjaer can be content to let his side's form on the pitch do most of the talking.
Victory on Sunday would lift Man United 12 points clear of fifth place with only six games of their season remaining and, with Liverpool and Leicester City the only teams in the current top nine still to face this term, they would be confident of completing the job fairly comfortably from that position.
Even if there is a remarkable collapse in the final throes of the campaign, the Red Devils have another increasingly-promising route into the Champions League next season having booked a Europa League semi-final meeting with Roma courtesy of a 4-0 aggregate triumph over Granada.
Man United secured their progress with minimal fuss, winning both legs 2-0, but they have not made things quite as easy for themselves in the Premier League in general.
Last weekend's win over Spurs was the ninth time they have come from behind to win in the top flight this term - only Newcastle in 2001-02 have produced more comeback wins in a season in the competition's history - while it also took them up to 28 points rescued from losing positions - take those away and Man United would sit 14th, just two points above Burnley.
While Solskjaer will want to avoid falling behind so often, if it happens again this weekend then they will be confident of turning it around once more, particularly as Burnley have thrown away leads in both of their last two matches.
The Clarets were two goals to the good against Southampton before collapsing to a 3-2 defeat, and then last weekend lost 2-1 at home to Newcastle United despite leading with just over half an hour remaining.
Those defeats make it just one win in eight Premier League games for Burnley, although four draws in that time have kept them at arm's length of the relegation zone.
Dyche will know that they are not quite safe just yet, but their seven-point cushion over Fulham means that they are not in immediate danger either and five points from their final seven games should be enough to secure another season of Premier League football.
Whether Dyche will look back on that as another success is a different matter; the Clarets have already lost as many league games this season as they did throughout the whole of last term, while they are nine points worse off than at the same stage of 2019-20.
The Burnley boss has made no secret of his frustration at the lack of investment in the squad, though, and with survival their number one priority every season, he will no doubt be content to beat the drop once more.
Burnley arrive at Old Trafford not only with a good record at the ground, but having also already won at the likes of Arsenal, Liverpool and Everton in the league this season.
Overall their away record this term has not been good - only two teams have picked up fewer points on the road - but they have alternated between wins and defeats in away games since the turn of the year and, if that pattern continues this weekend, then they would claim another famous triumph at Old Trafford.
Marcus Rashford was left on the bench during Thursday's second leg against Granada due to a slight fitness concern, but he is expected to recover in time to start this match.
That could mean that Mason Greenwood drops out of the starting XI again, despite scoring in both of his last two Premier League appearances.
Man United could be without Anthony Martial until the end of the season after he suffered a sprained knee while away on international duty with France.
Edinson Cavani has stepped up to lead the line in his absence, though, and the Uruguayan's form has led to more calls for him to extend his stay at the club.
Luke Shaw and Harry Maguire should return to the starting XI after missing out in midweek through suspension, while Scott McTominay and Dean Henderson - the latter of whom appears to have leapfrogged David de Gea as Solskjaer's first choice goalkeeper - will also be pushing for recalls.
Burnley, on the other hand, are sweating over the fitness of Nick Pope, whom Dyche admitted was "touch and go" for the game as he continues to recover from a shoulder injury.
The Burnley boss may decide to keep faith with the two who started against Newcastle, though, with Chris Wood having scored in his last two Premier League visits to Old Trafford and Matej Vydra having netted three times in his last five top-flight outings - as many as he had in his previous 53 before that.
Manchester United possible starting lineup:
Henderson; Wan-Bissaka, Lindelof, Maguire, Shaw; Fred, McTominay; Rashford, Fernandes, Pogba; Cavani
Burnley possible starting lineup:
Peacock-Farrell; Lowton, Tarkowski, Mee, Pieters; Gudmundsson, Brownhill, Westwood, McNeil; Wood, Vydra
We say: Manchester United 1-0 Burnley
Burnley's record at Old Trafford in recent years should not be ignored and they will go into this game more confident of getting something from the game than they might be under normal circumstances.
However, it is difficult to look past a Man United team in good form and with Champions League football next season within their grasp.
It may not be a classic, but we expect the home side to come away with another big three points.
Watch the Sports Mole Football Shorts prediction for this game below: