Pep Guardiola's City side have an eight-point lead at the top and have yet to taste defeat in the league, while Jose Mourinho's United have lost twice this year.
Over the years there have been some thrilling clashes between the two and a win for City would extend their lead to 11 points and certainly damage their rivals hopes of claiming silverware in May - but a win for United would throw the title race wide open.
Mourinho's men have had a few minor slips this season with defeats at Huddersfield Town and Chelsea but their home form have been impressive.
The Red Devils have claimed 21 out of a possible 21 points at Old Trafford this year scoring a total of 20 goals and defining why the Theatre of Dreams was once called a 'fortress.'
United are full of confidence having dispatched Arsenal last weekend by securing a 3-1 win in North London. Just like their Manchester-rivals, they too finished top of their Champions League group.
Coming into the anticipated encounter, City are obviously favourites to steal the win as a result of them having a superior lead at the Premier League summit. Guardiola's side boast an eight-point margain and have yet to be beaten this season.
However, the Blues did fall to their first defeat in all competitions this past week when they were beaten 2-1 by Shakhtar Donetsk in the UEFA Champions League. Although it didn't affect proceedings in Group F as City were already winners, they'll be desperate to return to winning ways at Old Trafford.
The visitors have won 14 of their 15 league games this season and have only dropped two points - a 1-1 draw with Everton back in August.
Having already secured away victories against Chelsea and Napoli in their impressive start a win at United will be a statment towards their ambitions in the league and Europe.
The Manchester-derby has thrown up many memorable moments, from Wayne Rooney's sensational over-head kick to City's 6-1 demolition of United.
During last-season, when Guardiola and Mourinho met for the first time since the Madrid-Barcelona days it was City who had the edge. When the pair met in this fixture last year, Kevin De Bruyne and Kelechi Iheanacho scored for City while Zlatan Ibrahimovic was on the scoresheet as the Reds fell to a 2-1 defeat.
In the return fixture, the pair played out a 0-0 draw at the Etihad Stadium, with Marouane Fellaini's red-card the real talking point of the game.
When it comes to encounters, United have the edge as they've secured victory on 72 occassions, while City have their 52 wins against their rivals.
The big news for Mourinho's men is that Paul Pogba will be unavailable for selection after the midfielder starts his three-game suspension after being sent off at The Emirates last weekend, and joins Michael Carrick and Eric Bailly on the sideline.
However, there is a boost for United as Nemanja Matic, Phil Jones and Ibrahimovic are all expected to be named in the matchday squad, while Fellaini will be assessed ahead of kick-off.
As far as City are concerned, David Silva (who was rumoured to miss out in the derby) will be an option for Guardiola at Old Trafford after overcoming a small knock.
However, skipper Vincent Kompany is likely to play no part on Sunday afternoon with Nicolas Otamendi and Eliaquim Mangala expected to start at the back.