The Red Devils have drawn three of their last four league games and are now 10 points adrift of leaders Manchester City, while Newcastle are six points above the relegation zone.
Last week's 1-1 draw at strugglers West Bromwich Albion was surely the final nail for United's title aspirations, particularly after City won their game in hand in midweek.
The 10-point gap Ole Gunnar Solskjaer's men have to make up on the leaders is fast becoming insurmountable, but United are not ready to throw in the towel just yet.
Solskjaer will certainly be hopeful that Thursday's 4-0 win over Real Sociedad in their Europa League last-32 first leg can provide a catalyst to push on in the league.
A place in the last 16 of the Europa League now all but guaranteed, and an FA Cup quarter-final with Leicester City to come next month, Solskjaer's focus is now on the league.
United's only win in their last six league matches was their record-equalling 9-0 thumping of Southampton - a performance in stark contrast to last week's draw with West Brom.
Finding that consistency is now the aim for Solskjaer, and this weekend's visit of Newcastle provides a chance to get three more points on the board.
Newcastle have won just one of their last 35 away league games with Man United, losing 25 of those, including four of their last five visits to Old Trafford.
The Magpies have alternated between a win and defeat in their last five games, most recently following up a 3-2 win against Southampton with a 2-0 loss at Chelsea last Monday.
Steve Bruce was without Callum Wilson for that trip to Stamford Bridge and will have to make do without the striker for at least another six weeks.
That is worrying news for Newcastle, having lost all three Premier League games without scoring when Wilson has been absent this season.
With Fulham picking up another point in midweek, and the Cottagers facing bottom side Sheffield United next, Newcastle's six-point gap on the bottom three could shrink further with another loss on Sunday.
Manchester United Premier League form: WLDWDD
Manchester United form (all competitions): DWDWDW
Newcastle United Premier League form: LLWLWL
Newcastle United form (all competitions): LLWLWL
Scott McTominay is another who is expected to miss out after aggravating a knock in midweek, but Solskjaer still has a few options to choose from in the holding midfield position.
Rashford has been involved in six goals in his six Premier League appearances against Newcastle (three goals, three assists), scoring one and assisting two in Man United's 4-1 win in the reverse fixture.
Manchester United possible starting lineup:
De Gea; Wan-Bissaka, Lindelof, Maguire, Shaw; Fred, Matic; Greenwood, Fernandes, Rashford; Cavani
Newcastle United possible starting lineup:
Darlow; Krafth, Lascelles, Clark, Lewis; Willock, Hayden, Shelvey; Almiron, Gayle, Saint-Maximin
We say: Manchester United 2-0 Newcastle United
Man United may not be in the best of form in the Premier League, but they showed against Real Sociedad on Thursday exactly what they are capable of on their day.
Newcastle have won just two of their last 13 games and, given their terrible record in this fixture - only against Liverpool (81) have they lost more Premier League fixtures than against Man Utd (80) - we can only see this game ending one way.
Watch the Sports Mole Football Shorts prediction for this game below: