It should be a fascinating night and ahead of the game, we spoke to Rob Dawson, ESPN's United correspondent, to get the inside track on the Old Trafford side.
What’s your assessment of United’s season so far?
They have been inconsistent. There have been some very good performances and results and some very bad ones.
Finishing second in the Premier League would represent progress and adding the FA Cup would add a shine to the season.
Still, a club of United's size begin every season thinking about winning the title and the Champions League and they have fallen short in both competitions. That's something Jose Mourinho will hope to fix next season.
What can we expect from United tactically on Saturday?
Mourinho will hope to make it a tight game that comes down to who makes the fewest mistakes. It's often the way he has approached big games away from home. United won't be afraid to let City have the ball and then hope to make the most of their chances to break. Romelu Lukaku's ability to be a focal point up front will be key, as will the pace of Marcus Rashford and Alexis Sanchez either side.
Who’s the man City need to watch?
Lukaku is in good form. He had a good start to the season and then had a bit of a dip. But he's scored 11 in his last 15 games and three in his last three. He's got a good record against City and scored at the Etihad Stadium for Everton last season. He will fancy his chances of getting another one on Saturday.
What have you made of City this term?
Fantastic. You don't blitz the Premier League like they have this season without being a very good team. They will be worthy champions when it happens. Obviously, the result at Liverpool on Wednesday was a set-back, but it says a lot about how good they have been going forward this season that, even at 3-0 down, barely anyone thinks the tie is over.
Who is the player United should fear most?
David Silva. Kevin De Bruyne, quite rightly, has got a lot of attention this season, but Silva has been magnificent, too. In any other season he would be a shoe-in for player of the year. He has hurt United plenty of times in the past and they will have have to find a way of dealing with him if they want to win this weekend. Clearly, though, that's easier said than done.
United have lost eight of the last 13 Manchester derbies. Do you think there’s now a bit of nervousness ahead of these games in the United dressing room?
It's not a great recent record, but there won't be any nervousness in United's dressing room. The players will see it as a chance to give the fans something to shout about and perhaps, lay down an early marker for next season. Their main aim next season will be to win the title so they will be keen to prove the gap between the teams isn't as big as the table suggests.
De Gea, Valencia, Young, Smalling, Bailly, Matic, Pogba, Lingard, Rashford, Sanchez, Lukaku.
Rob Dawson is Manchester United correspondent for ESPN. You can follow him on Twitter: @RobDawsonESPN