Elsewhere, Liverpool will seek to make it seven league wins in seven against high-flying West Ham, one of only two sides to beat the Reds this season.
Arsenal could take advantage of visits to the top two for the Hammers and United by moving into fourth with games in hand to come when they travel to Watford.
AFP Sport takes a look at some of the key talking points ahead of the weekend action.
Can City end United Etihad jinx?
Even though they are now indisputably the top dogs in Manchester, City have had real problems beating United on their own turf in recent years.
The Premier League champions have won just one of their past seven home games in all competitions against United — in sharp contrast to their impressive record at Old Trafford.
Both teams need the three points on Sunday, with leaders City seeking to keep Jurgen Klopp’s charging Liverpool at arm’s length and United’s top-four hopes looking shaky.
The fourth-placed Reds are just two points ahead of West Ham and Arsenal as they seek to secure Champions League qualification for next season, while the Gunners have three games in hand.
City, who tend to dominate possession, have been caught out in recent years by United’s pace on the break and Pep Guardiola will be wary of the threat posed by players such as Jadon Sancho and Marcus Rashford.
United have lost just one league game since interim manager Ralf Rangnick took charge in December but this is by far his toughest task yet.