While Sunday sees North-East rivals Sunderland and Newcastle United go head to head and Jurgen Klopp take charge of Liverpool for the first time at Anfield in the Premier League, the biggest match will be taking place at Old Trafford.
It will be the 37th Premier League meeting between the rivals and here Sports Mole has picked out the top five that have been played out at the home of United.
1. Man United 5-0 Man City (1994)
To this day Sir Alex Ferguson regards the events of September 23, 1989, as one of his most harrowing days in management. Already under fierce pressure, the Scot watched on powerless as his United side were hammered 5-1 by City at Maine Road. There were suggestions at the time that Ferguson would pay for that result with his job, but the board kept faith.
He would go on to gain some revenge five years later in a match that would be regarded as Andrei Kanchelskis's finest in a United shirt. The Russian winger scored what remains the fixture's last hat-trick, while Eric Cantona and Mark Hughes also weighed in with goals as the Red Devils ran riot.
2. Man United 1-1 Man City (2001)
Roy Keane's actions mean that people very rarely remember anything else from this encounter, let alone who scored the goals. For the record, the recently-named Footballer of the Year Teddy Sheringham put United in front from the penalty spot after Paul Scholes had earlier failed to do so from 12 yards. Yet, the spoils would be shared after Steve Howey flicked in Paul Dickov's corner six minutes from time.
However, the headlines belonged to United's captain. Four years earlier Alf-Inge Haaland, then of Leeds United, had stood over the Irishman accusing him fof eigning injury when he had in fact snapped his cruciate ligament. It was a moment that was still evidently on the midfielder's mind when he planted his studs into Haaland's right knee, earning him a red card from referee David Elleray. Writing about the incident in his most recent autobiography last year, Keane said: "There are things I regret in my life and he's not one of them."
3. Man United 4-3 Man City (2009)
During his three seasons as a United player, Owen scored just five Premier League goals. But when one of those is a stoppage-time winner against City, the relatively low contribution can be easily overlooked. Before the former Liverpool and Real Madrid man got in on the act, though, the two teams played out a six-goal thriller.
Wayne Rooney and Darren Fletcher (twice) put the home side in front on three occasions, but Gareth Barry and a brace from Craig Bellamy looked to have secured the Citizens a point. However, with the clock having ticked beyond the allotted stoppage time, Ryan Giggs threaded a pass through for Owen, who having taken one touch then beat Shay Given with the outside of his right boot.
4. Man United 1-6 Man City (2011)
If 1989 was Ferguson's lowest moment in management, this must have been a close second. Mario Balotelli, who opened the scoring and then revealed the famous 'Why Always Me' T-shirt, was the City hero. It was only 1-0 to Roberto Mancini's charges at the break, but following the 47th-minute sending-off of United defender Jonny Evans, the hosts lost all their composure.
Balotelli added a second on the hour mark, before Sergio Aguero got in on the act. It seemed that Fletcher had added a consolation goal and some respectability to the scoreline for United in the 80th minute, but a late double from Edin Dzeko and another goal from playmaker David Silva inflicted a biggest home defeat on United since February 1955.
5. Man United 0-3 Man City (2014)
"I think we've played a very good side and it's the sort of standard and level we need to try and aspire to get ourselves to at this moment in time." With those words, David Moyes all but hammered the final nail into the coffin of his Man United tenure. Having seen Liverpool control proceedings at Old Trafford a few days earlier, United fans were forced to endure more of the same when City came calling.
Dzeko scored their first goal with only 45 seconds played, by which time the visitors had already spurned two good opportunities. The Bosnian then scored his and City's second goal in the 56th minute when he got ahead of Rio Ferdinand to volley in Samir Nasri's corner. It was Yaya Toure that rubbed further salt into the wound one minute from the end, much to the disbelief of the home faithful. Moyes's post-match thoughts hardly helped matters and unsurprisingly he lasted just three more games before the axe was wielded.