The hosts come into the match now sitting sixth in the Premier League table with a game in hand over most of the teams around them, while Leeds were big winners against Newcastle United last time out.
A first league meeting between these two sides for more than 16 years will inevitably evoke memories of the fierce battles this rivalry has thrown up in years gone by, and there is no doubt that this fixture is one of those which the Premier League missed most during Leeds' absence.
For Leeds fans looking for a good omen ahead of their long-awaited league trip to Old Trafford, this match comes on the 90th anniversary of their biggest ever victory over Man United - a 5-0 win at Elland Road in 1930.
Leeds also memorably won on their last visit to Old Trafford almost 11 years ago, when Jermaine Beckford fired the then-League One outfit to victory over a side that had made it to the Champions League final the previous year.
Another triumph for the visitors on Sunday would be nowhere near as big a shock as that, but it would certainly defy the history of this fixture, with Man United having lost just one of their last 13 top-flight games against Leeds.
At home, Man United have played more Premier League games against Leeds without losing than against any other club, with the Whites' last league triumph at Old Trafford coming way back in February 1981 - 15 games ago.
Old Trafford is by no means the fortress it used to be at the moment, though, with the Red Devils having won just one of their last eight Premier League games on their own patch.
Only three teams have picked up fewer points at home all season, and perhaps even more worrying is the fact that only Burnley have scored fewer home goals than Man United's measly tally of three from six games so far.
Just one of those goals has come in their last four home outings too, and should that drought continue this weekend then Man United would equal an unwanted club record of failing to score more than once in eight consecutive top-flight matches - something they have only done once before, and that was way back in 1920.
In spite of that, Man United's league position remains relatively strong; the sixth-placed Red Devils are only two points adrift of second-placed Tottenham Hotspur and boast a game in hand over every other team in the top half apart from Manchester City.
Indeed, while their home form will be a concern, their faultless away record means that they have now picked up 16 points from the last 18 on offer in the league, leaving them top of the form table despite Ole Gunnar Solskjaer finding himself under pressure once again.
Thursday night's 3-2 win over Sheffield United sparked more suggestions from within the squad that Man United could even be capable of a title challenge this season, although that theory is set to be tested over the packed Christmas schedule.
Solskjaer's men face Everton in the EFL Cup quarter-finals three days after this match before taking on Leicester City, Wolverhampton Wanderers and Aston Villa - a run of five games in the space of just 12 days.
Leeds' schedule is a little less hectic due to their elimination from the EFL Cup, while upcoming matches against Burnley and West Bromwich Albion immediately after Christmas mean that they can afford to focus fully on what is one of their biggest games of the season.
Inconsistency has been the issue for Marcelo Bielsa's side so far, with five wins and six defeats among their 13 outings, including just two wins from their last seven.
The most recent of those came on Wednesday night, though, as a late flurry sealed a 5-2 triumph over Newcastle United at Elland Road.
In a bizarre twist of fate, that is the third time they have scored five goals in their last league game before facing Manchester United, and the previous two also came against Newcastle at around Christmas time.
Leeds lost one and drew one of those subsequent meetings with the Red Devils, but will be hoping for even better than that on Sunday given their opponents' home woes this season.
The key to that could be keeping Man United's misfiring home attack at bay; Leeds' three away wins this season have all come alongside clean sheets, but when they have conceded they have gone on to ship four against Liverpool, four against Crystal Palace and three against Chelsea.
There has been plenty of entertainment in Leeds' away games so far, then, and there will be none bigger for them this season than this visit to their bitter rivals.
Sunday will be Marcelo Bielsa's third managerial meeting with Manchester United, and a good omen for Leeds fans is that he won the previous two - home and away with Athletic Bilbao in the 2011-12 Europa League.
Manchester United Premier League form: WWWWDW
Manchester United form (all competitions): WLWLDW
Leeds United Premier League form: LDWLLW
Manchester United could welcome Edinson Cavani back into their squad for this one after he missed a third successive game in midweek due to a muscle problem.
Dean Henderson's early howler against his former club may see David de Gea regain his place in goal, while Luke Shaw, Fred and Scott McTominay are among the other players who will be expecting to come back in.
It is a sign of the paucity of these showdowns in recent years that Paul Pogba made his senior club debut the last time the two sides met, with the then-18-year-old replacing Ryan Giggs off the bench in September 2011.
Pogba has spent plenty of time on the bench again this season, and like nine years ago has been linked with a move away as a solution, but he appears to be back in favour for Solskjaer now and could start for the third time in a week here.
Bielsa could name an unchanged side, although Pablo Hernandez is knocking on the door for a start following his two assists off the bench in the win over Newcastle.
Patrick Bamford should lead the line again, having netted nine goals in 13 Premier League games for Leeds so far.
Manchester United possible starting lineup:
De Gea; Wan-Bissaka, Lindelof, Maguire, Shaw; McTominay, Fred, Pogba; Fernandes; Martial, Rashford
Leeds United possible starting lineup:
Meslier; Dallas, Ayling, Cooper, Alioski; Phillips, Raphinha, Rodrigo, Hernandez, Harrison; Bamford
We say: Manchester United 1-1 Leeds United
Ask most Leeds fans which one match they would most want to win this season, and they would say this one. Getting one over their biggest rivals in their own backyard has been long overdue as far as they are concerned, and they have not even had the chance to do so for more than a decade.
They certainly have a realistic chance this weekend given Man United's poor home form, but it is difficult to know what to expect from Leeds at the moment and so we are going for a score draw between the old foes.
Top betting tip
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