Sir Alex Ferguson’s men travel to the Etihad Stadium with a three point advantage of the champions, who hope to build on two successive victories over the Reds last season.
Victory would provide a huge shot in the arm to either side’s title ambitions and would go a long way to appeasing the fans, who have been slightly critical of both teams this campaign.
Quite simply, this weekend’s 163rd Manchester derby is the biggest since, well, the last one. Which got us thinking: Which are the most memorable encounters between these two great clubs?
Here, I assess the options and recall five classic battles between City and United.
Each season, Manchester derbies are often billed as the biggest since 1974, when City travelled to Old Trafford knowing that a victory would send their great rivals down to the old Division Two.
Infamously, it was ex-Red and European Cup winner Denis Law who scored a now iconic back-heel to earn the Blues a 1-0 win, simultaneously casting United into the second tier of English football.
Such was his commitment and dedication to the Reds, the Scottish striker was inconsolable after netting and had to be substituted as a result. To this day, the goal still haunts the Lawman.
Two Niall Quinn headers gave City a commanding lead at Maine Road, where the Citizens looked good to go on to seal a convincing and memorable victory in the Manchester derby.
However, Eric Cantona, recently signed from rivals Leeds the season before, was not ready to lose, and almost singularly dragged United back into the game with a brace of finely taken goals.
Then, new signing Roy Keane, brought into from Nottingham Forest, cemented his place in Reds folklore by smashing home a late winner to seal a remarkable and, at times, inconceivable victory.
The signing of Michael Owen, a former Liverpool star, had raised eyebrows around Old Trafford when first announced in the summer of 2009, with many questioning the decision.
But with one poke, a right boot, the diminutive striker instantly won over his critics with a climatic, 96st minute winner over Mark Hughes’ City at the Theatre of Dreams.
Prior to Owen’s winner, the match had already had the makings of a classic thanks to goals from Darren Fletcher (two), Wayne Rooney, Craig Bellamy (two) and Gareth Barry.
Four months after Michael Owen’s stoppage time winner, City had replaced manager Mark Hughes with Italian import Roberto Mancini and travelled to Old Trafford, a League cup semifinal showdown.
United lost 2-1 in the first leg at Eastlands, and with just seconds remaining in the return fixture, the match was heading into injury time with the aggregate score level at 3-3. Nerves were jangling.
Until, Wayne Rooney popped up with another late winner, ghosting into the penalty area to head Ryan Giggs’ whipped cross past the helpless Shay Given, sending the Reds to Wembley.
Although a fixture, every United fan wants to forget City’s now infamous mauling of the Reds at Old Trafford, and it has become emblematic of the recent power surge from the Etihad Stadium.
The match was billed as the first true test of Roberto Mancini’s side’s title credentials and, unfortunately, the Blues delivered in spades, sweeping their opponents aside in clinical fashion.
Admittedly, a red card to Jonny Evans early in the second half did not help matters for Sir Alex Ferguson’s men, who ultimately paid the price for being too offensive with only 10 men on the pitch.