The two sides' encounters have seen dramatic comebacks, classic goals and controversial moments, but without wanting to spoil what lies ahead, I'll save the specifics for later.
This weekend sees two of the Premier League's elite teams lock horns once again, with White Hart Lane the battleground.
Here are the most memorable encounters and specific moments in recent years.
Date: 30 Oct, 2010
Final Score: 2-0 Man Utd
First on the list is Nani's strike past a confounded Heurelho Gomes back in 2010.
In one of the most bizarre moments in Premier League history, the hapless keeper rolled the ball out of his six-yard box for an apparent free kick, but referee Mark Clattenburg had instead motioned for play to continue after the ball had struck Nani's hand in the penalty area.
Sensing Christmas had come early, the Portuguese winger stroked the ball into an empty net to extend the Red Devils' lead to 2-0.
Then-Tottenham boss Harry Redknapp described the goal as "farcical" in his post-match interview.
On reflection, the error was mostly on Gomes' part as Clattenburg had never blown his whistle for the offence.
Date: 29 Sep, 2012
Final Score: 3-2 Tottenham
Earlier this season, Spurs claimed a thrilling 3-2 win on United's turf thanks to a Jonny Evans own-goal and strikes from Gareth Bale and Clint Dempsey.
It was Bale's effort though that truly sent shockwaves through the Old Trafford crowd.
Comebacks have quickly become a staple of Sir Alex Ferguson's side's current season, so when Tottenham took the lead after only two minutes in the 2012 fixture, one could be forgiven for thinking little of it.
But the flying Welshman's cracker on the half-hour mark capped off a truly one-sided first half, highlighting everything that was flawed with United's defence.
Receiving the majority of blame in the wake of the game was Rio Ferdinand, who was mercilessly mocked for how easily he was bypassed by Bale.
Date: 25 Apr, 2009
Final Score: 5-2 Man Utd
Like the game referenced in the previous slide, Manchester United had fallen behind to Tottenham having conceded two first half goals in a 2009 meeting, but on this occasion the Red Devils were able to complete a thrilling comeback.
A controversial penalty conceded by Heurelho Gomes jumpstarted United's afternoon, followed by a smartly taken Wayne Rooney effort.
But it was Cristiano Ronaldo who scored his team's all-important third, diving to head a low cross into the roof of the net.
Another Rooney strike and a scrambled Dimitar Berbatov tap-in put the gloss on a win that eventually proved crucial to United's title-chasing hopes.
Date: 29 Sep, 2001
Final Score: 5-3 Man Utd
Manchester United turned a three-goal half-time deficit into a 5-3 win in a howitzer of a game in the 2001/02 season.
Tottenham were cruising at home with new signing Dean Richards, Les Ferdinand and Christian Ziege finding the net in the opening 45 minutes..
But United came out roaring in the second half as Andy Cole, Laurent Blanc, Ruud van Nistelrooy, Juan Sebastian Veron and David Beckham all scored to stun the White Hart Lane faithful.
If the Red Devils hadn't scored twice in stoppage time to beat Bayern Munich in the Champions League final two years earlier, this result may just rank as the greatest comeback of Sir Alex's reign.
Date: May 27, 1999
Final Score: 2-1 Man Utd
The most memorable moment in clashes between Tottenham and Manchester United though has to be the latter club's Premier League-clinching victory on the final day of the 1998/99 season.
On a day when only victory would guarantee the Red Devils the title, the Old Trafford crowd were left stunned when Les Ferdinand opened the scoring early in the first half.
But a classic David Beckham curler and a delightful Andy Cole lob calmed nerves before a nail-biting final few minutes.
United emerged the winners of the game, claiming the first of what would eventually be an unprecedented trio of trophies.
The famous treble-winning season is unlikely to ever be replicated by an English club, let alone completed in such dramatic fashion.
What moment in past Manchester United vs. Tottenham Hotspur clashes would you consider the most memorable?