After a highly disappointing home defeat to Crystal Palace in their opening match of the season, United bounced back with back-to-back away wins against Brighton.
But with the chance to build some real momentum heading into the international break, they were handed a crushing blow by a Spurs side who claimed their third wins in six days in emphatic style.
Ole Gunnar Solskjaer's side now sit in 16th place after two defeats from three, and with Donny van de Beek their only high-profile signing this summer, all eyes will be on Old Trafford on Monday as the transfer window draws to a close.
Edinson Cavani and Alex Telles are both expected to complete their moves before the 11pm deadline, but with 11 goals conceded in three league games, there are serious problems for Solskjaer to solve.
Of course, with such a damning result, there were a number of key figures trending throughout the match. We take you through the most notable below...
Pochettino for Man United?
With Solskjaer enduring a tough start to the season, it's perhaps no surprise talk of Tottenham's former manager Mauricio Pochettino has resurfaced once more.
The Argentine is perpetually linked with a move to Old Trafford, and with United suffering an embarrassing defeat to rivals Spurs, there were countless calls for Pochettino to replace the Norwegian, and soon.
Pochettino has been out of action since November, when he was sacked by Spurs. How ironic it would be if his successor Jose Mourinho inflicts the crucial defeat on United to hand him another job.
Alas, talk of a Pochettino takeover is perhaps premature, but you feel his name will be synonymous with Solskjaer's for however long he is still in the job.
United should be using this an excuse to bring in Pochettino.
— Miguel Delaney (@MiguelDelaney)
Woodward must back Solskaer
Ed Woodward's relationship with the United faithful has been turbulent for some time now, but it's perhaps at its most strained after the crushing defeat.
Donny van de Beek is United's single high-profile signing this summer, and while Solskjaer has prioritised a move for Jadon Sancho throughout, a move now seems highly unlikely.
As stated, Cavani and Telles are expected to make their moves before Monday's deadline, but many are questioning whether that's what United actually need.
Luke Shaw, though struggling against Spurs, has been a consistent performer, while a 33-year-old Cavani - on massive wages - feels to many like a panic buy.
Cavani and Telles are not gonna fix this mess btw, don't be fooled. Glazers & Woodward Out till the end.
— RiZzy🔴 (@RiZzyUTD)
Neville and Evra furious
Evra went as far as to say that some United players needed a "slap", questioning what had happened to the side he once played for. The Frenchman insisted Solskjar has to be backed, however, saying he feels sorry for the Norwegian.
Neville also expressed his sympathy for Solskjaer, believing United are in a "repetitive cycle" of managers not being backed before they receive the sack.
The Sky Sports pundit blasted United's players, describing them as "absolutely pathetic, spiritless and spineless".
I hope the #mufc players, staff and board listen to what Patrice Evra and Gary Neville are saying on Sky. Former full-backs not holding back. They're angry, and they've every right to be. They fought for that shirt, they still care and that performance was unacceptable. #MANTOT
— Henry Winter (@henrywinter)
Where was Roy Keane?
What a day not to have Roy Keane in the studio, eh?
Many fans, perhaps not of Manchester United, were left highly disappointed by Roy Keane's absence, as you could bet your bottom dollar he'd have had a word or two to say about their performance.
The pundit, who has been particularly critical of Paul Pogba, would have likely had a field day as the Frenchman was dominated by a midfield three of Pierre-Emile Hojbjerg, Moussa Sissoko and Tanguy Ndombele.
Gutted there’s no Roy Keane in the studio! 😡⚽️
— Curtis Woodhouse (@curtiswoodhous8)
Erik Lamela receives some hefty criticism
Though Tottenham were creating all sorts at 2-1 up, a decisive moment came as Anthony Martial was harshly sent off for taking a swipe at Erik Lamela, who made a meal of the contact as he flung himself to the floor.
Spurs went on to score four more to no reply, and it's fair to say, Solskjaer wasn't best pleased with his actions.
🗣"If that was my player I would have hung him out to dry"
Ole Gunnar Solskjær was not happy with the Martial red card and Erik Lamela's reaction pic.twitter.com/MBfO1iDo3R
— Football Daily (@footballdaily)
The Kane and Son show continues
The pair seemingly have a telepathic relationship and were once again at it at Old Trafford. No player has more than Son's six Premier League goals, and no one has more than Kane's six assists.
They are absolutely on fire!
— Tottenham Hotspur (@SpursOfficial)
Mourinho comes back to haunt United
Well, what can you say about Jose Mourinho? The guy just can't keep himself away from the headlines.
Mourinho insisted finishing second and winning the Carabao Cup and Europa League was his biggest achievement in football, and it appears that claim may have some validity.
The three-time Premier League winner endured a tricky start to life in Tottenham, but he's got his side playing well now. And with Gareth Bale to come into the side, it's looking frightening in north London.