Ole Gunnar Solskjaer's future was thrown into jeopardy on Sunday afternoon following a humbling, humiliating 6-1 defeat at home against Tottenham Hotspur.
A trouncing of this ilk had been on the cards since the season got underway and it seemed rather ironic that Mourinho, a manager who was lambasted for his negative style of football during his stint at Old Trafford, was the architect behind a free-scoring performance from the north London visitors.
The result reignited discussion regarding Solskjaer's ability to manage a star-studded and historic club with such lofty expectations, as the club continue to falter in light of Sir Alex Ferguson's retirement.
Under Fergie's watch, United were notoriously hard to beat and revered for their never-say-die spirit, but that mentality has eluded the club since the Scot called time on his career.
Most concerningly for the Red Devils, the manner in which they capitulated on Sunday was by no means an aberration.
Here, we rank United's 10 most humiliating and significant defeats of the post-Ferguson era.
10. Man United 1-2 Sevilla (13/03/2018)
Having drawn 0-0 away at Sevilla in the first leg of a last-sixteen Champions League tie, United needed a home win to progress into the quarter-finals of the Champions League.
But rather than chase the victory, Jose Mourinho's side were lethargic in possession, refused to take risks and showed little desire to take the game to the visitors.
On a bizarre evening that suggested Mourinho's tried and tested methods had run their course, Wissam Ben Yedder scored a quick-fire brace from the bench in the space of four second half minutes.
For a club of United's stature, the manner in which they were dumped out of Europe's most prestigious knockout competition was a telling sign of the new times.
9. Everton 2-0 Manchester United (04/04/2014)
Moyes' final game in charge of United arrived against his former club.
His successor, Roberto Martinez, continued to solidify his status as one of the best up-and-coming managers in European football as his side ran out two nil winners.
Though the scoreline was not overly damming, the fact Moyes was defeated by his former employer shortly after losing games against Man City and Liverpool underlined the sizeable mistake United had made with his appointment.
8. MK Dons 4-0 Man United (26/08/2014)
One of football's cult heroes, Will Grigg, was the protagonist behind MK Dons' thumping 4-0 win over United in a League Cup 2nd round tie in August 2014.
Grigg scored a brace as the League One outfit welcomed Louis van Gaal to English football and laid bare the size of the task at hand.
United were not at full strength for the occasion but had more than enough quality on the field to progress against League One opposition.
7. Man United 0-3 Spurs (27/08/2018)
The night when Lucas Moura announced himself to English football revealed the gulf in class between Spurs, a club in the ascendancy under Mauricio Pochettino, and a United outfit in danger of being left behind with Mourinho at the helm.
That the result arrived so early in the season on matchday three was of particular concern for the fans and boardroom alike, and Mourinho failed to recover from the defeat before being dismissed in December.
6. Man United 0-3 Manchester City (25/03/2014)
Having already been embarrassed in his first Manchester derby as United manager, the return fixture at Old Trafford offered Moyes an opportunity for redemption.
Edin Dzeko's first minute opener, however, dashed any hopes of a home win. Dzeko added another in the second half before Yaya Toure wrapped up the points with a third in injury time.
Given the level of humiliation associated with a 3-0 home derby defeat, it's no surprise Moyes was dismissed just a month later.
5. Everton 4-0 Man United (01/04/2019)
A 4-0 loss at Goodison Park was Solskjaer's highest scoring defeat prior to Tottenham's rampant win at Old Trafford.
The result arrived just a few weeks after the Norwegian had signed a three-year contract with the club having impressed during his stint as caretaker, but the drubbing on Merseyside raised doubts about the club's decision to reward him with a long-term deal.
4. Man United 1-6 Tottenham Hotspur (04/10/2020)
United's most recent entry on the list is also the heaviest defeat of the lot.
While this was clearly a deeply forgettable afternoon for the club, the fact they played the game behind-closed-doors, and spent a large portion of the game with ten men, has kept this result out of the top three.
3. Man United 0-3 Liverpool (16/03/2014)
Big performances in derby games against City and Liverpool may have done something to salvage Moyes' humbling time in charge of the Red Devils, but his side reserved their meekest displays for their historic rivals.
The Reds rocked up at Old Trafford and scored three goals without return. Steven Gerrard was at the heart of it, scoring twice, and Luis Suarez combined with Daniel Sturridge to add some gloss to a complete away performance.
2. Chelsea 4-0 Man United (23/10/2016)
This was a defeat of equal significance for United and Mourinho. Back at his old club, the Portuguese manager was outthought and outclassed by a wildly gesticulating Antonio Conte.
A 3-5-2 system, which was rarely deployed in the Premier League until Conte popularised the approach, stifled United's attacking endeavours and Chelsea ran riot at Stamford Bridge with goals from Pedro, Gary Cahill, Eden Hazard and N'Golo Kante.
1. Man City 4-1 Man United (22/09/2013)
Welcome to Manchester, David Moyes. The first derby fixture of the season would have been bookmarked as an early indicator of the Scots' potential to build on Ferguson's legacy. By the 50th minute, the new reality had begun to dawn upon both sets of supporters: the pendulum was swinging from red to blue.
A Sergio Aguero brace was supplemented with goals from Yaya Toure and Samir Nasri as a dominant City side swaggered into a 4-0 lead. Wayne Rooney added a consolation goal with a sumptuous free-kick in the 87th minute, but his goal did nothing to alter the significance of the result.
With the derby humiliation the tone was set for the new era: a significant chapter had ended, and with it United's unprecedented period of domination was left consigned to the history books.