Victory would see Pep Guardiola's side match Real Madrid for the fourth-longest winning run, 22 games, by top-flight clubs worldwide – trailing only Bayern Munich (23), Ajax (26) and Guinness world record holders The New Saints (27).
Here, the PA news agency analyses the differences between the Premier League's top two this season.
City's dominance this season has been built from the back, with 15 clean sheets – two more than any other top-flight club, and five more than United.
That corresponds to a 71 per cent save rate, with 17 goals conceded from 59 shots on target – United have conceded 32 from 100, saving an easy-to-calculate 68 per cent.
The signing of Ruben Dias and the resurgence of John Stones in partnership with him means Guardiola has had the luxury of Aymeric Laporte as a back-up central defender, while Joao Cancelo is free to maraud upfield from his nominal full-back position.
The ever-present Harry Maguire has allowed United full-backs Luke Shaw and Aaron Wan-Bissaka to also contribute in attack but they have been reliant on Victor Lindelof alongside him, with only Axel Tuanzebe and the injury-prone Eric Bailly in reserve.
Manager Ole Gunnar Solskjaer has been keen to write off the 11 goals conceded in the season's first three games, and Bailly replaced Lindelof for the 6-1 loss to Tottenham in that time.
City are the league's top scorers with 56 goals, three more than United – though Solskjaer's side have actually been more clinical with their chances.
With 418 shots, City have needed 7.46 attempts per goal compared to 7.19 for United, whose 381 shots ranks behind Liverpool (399) in third in the league.
Both teams' top scorers are operating in central midfield, Ilkay Gundogan with 11 for City and Bruno Fernandes 15 for United.
Gundogan has been the major beneficiary of Guardiola's use of a 'false nine' with Sergio Aguero absent for much of the season, while Fernandes' total is inflated by penalties.
Indeed, if spot-kicks are excluded, City have the top-flight's leading scorer over the past two seasons in Raheem Sterling, with 29 goals from open play.
Liverpool's Mohamed Salah and Southampton's Danny Ings are his nearest challengers in that regard with 27 apiece – penalties lift Salah's total to 36 and Ings' to 30 – while United's leading scorers are Anthony Martial with 21 and Marcus Rashford on 20, with the England striker adding six penalties last season.