The Blues head into the game on the back of 13 successive league wins, knowing a Premier League record-equalling fourteenth would extend their lead at the top of the table to 11 points.
With pride as well as points at stake, we spoke to the ESPN's Rob Dawson to get the inside track on United.
What's your assessment of United’s season so far?
They've made a good start.
They're mounting a serious title challenge for the first time since Sir Alex Ferguson retired and they have improved drastically from last season when they finished sixth. On top of the that, they walked their Champions League group on their return to the competition.
All in all, it has been a positive start.
Who has been the stand-out player?
Paul Pogba has been good in the games he's played but he's missed a big chunk of the season through injury.
Nemanja Matic, Antonio Valencia and David De Gea have all been very consistent.
The most improved player has been Anthony Martial. He's looked like the player who first arrived from Monaco after a dip last season.
What have you made of the job Jose Mourinho's done?
Very good. He won two trophies in his first season and looks like he's building on it this season.
It has been a long time since United have been considered a serious title contender, or a team that can get to the latter rounds of the Champions League, but Mourinho has got them there.
Ultimately, he will be judged on whether or not he can win the title, but he has certainly made progress.
What do you think United’s approach will be?
They will have to attack because it is a game they really need to win.
That won't mean throwing everyone forward and United will be happy to soak up pressure when they have to. But they will have to try and hurt City, as well.
United need City to drop points but they can't expect other teams to do it for them and not take care of the things they can control.
How much of a loss is Paul Pogba?
Big. He missed the games against Tottenham, Liverpool and Chelsea because of injury. In the one he did play against Arsenal he was outstanding before he got sent off.
The difficulty for Mourinho is that there is no like-for-like replacement. They have got other central midfielders but no one can replicate his creativity from the centre of the pitch. It's a big miss.
What have you made of City this season?
They have been fantastic. To win 14 of your first 15 Premier League games is an incredible achievement and to do it playing the football they have is even more impressive.
I think Pep Guardiola has already proved a lot of people wrong who perhaps thought his brand of football would never work in the Premier League.
There is still a long way to go but they are the team to beat this season.
Predicted United XI?
De Gea, Valencia, Young, Smalling, Rojo, Matic, Fellaini, Herrera, Lingard, Martial, Lukaku.
You can follow Rob on Twitter: @RobDawsonESPN