Pep Guardiola's side are 16 points clear of the Red Devils coming into the game and a win would put them 19 points ahead with just six games left to play.
However, they will have to pick themselves up following a disastrous 3-0 Champions League quarter-final defeat to Liverpool on Wednesday, which leaves them with a mountain to climb.
Jose Mourinho and his charges have little chance of winning the league, but they will be desperate to avoid the humiliation of effectively handing the title over to the rivals.
|Game||Manchester City vs Manchester United|
|Date||Saturday, April 7|
|Time||17:30 BST / 12:30 ET|
|Stream (US only)||fuboTV (7-day free trial)|
TV Channel, Live Stream & How To Watch
In the United States (US), the game can be watched live and on-demand with fuboTV (7-day free trial).
New users can sign up for a free seven-day trial of the live sports streaming service, which can be accessed via iOS, Android, Chromecast, Amazon Fire TV, Roku and Apple TV as well as on a web browser.
|US TV channel||Online stream|
|NBC / Telemundo||fubo TV (7-day free trial)|
In the United Kingdom (UK), the game can be watched live on TV on Sky Sports Premier League and it can be streamed live online using Sky Go.
|UK TV channel||Online stream|
|Sky Sports Premier League||Sky Go|
Squads & Team News
|Position||Man City players|
|Goalkeepers||Ederson, Bravo, Grimshaw|
|Defenders||Walker, Danilo, Kompany, Laporte, Stones, Mendy, Adarabioyo, Otamendi, Duhaney|
|Midfielders||Sterling, Gundogan, De Bruyne, Delph, Sane, B. Silva, D. Silva, Fernandinho, Zinchenko, Toure, Foden, Diaz, Dele-Bashiru|
|Forwards||Aguero, Jesus, Nmecha|
Sergio Aguero remains a doubt for the match as he continues his recovery from a knee injury, while Benjamin Mendy is also working his way back to full fitness.
However, Fabian Delph could return to the starting XI.
Potential Man City starting XI: Ederson; Delph, Kompany, Otamendi, Walker; Gundogan, De Bruyne, Fernandinho, D. Silva, Sterling; Jesus.
|Position||Man United players|
|Goalkeepers||De Gea, Romero, Pereira|
|Defenders||Bailly, Blind, Darmian, Jones, Lindelof, Rojo, Shaw, Smalling, Valencia|
|Midfielders||Carrick, Fellaini, Gomes, Hamilton, Herrera, Lingard, Mata, Matic, McTominay, Pogba, Young|
|Forwards||Sanchez, Lukaku, Martial, Rashford|
Manchester United have no fresh injury concerns but are expected to be without Daley Blind and Sergio Romero.
Phil Jones, Marouane Fellaini and Marcos Rojo could all return though, giving Mourinho more options to choose from.
Potential Man Utd starting XI: De Gea; Valencia, Smalling, Bailly, Young; Matic, McTominay, Mata, Sanchez, Martial; Lukaku.
Betting & Match Odds
Man City are heavy favourites to win with dabblebet giving odds of 10/11. Man United are rated 3/1 bets while a draw is available at 11/4.
Man City could wrap up the Premier League title in record fashion on Saturday and such a scenario would represent a real changing of the guard in a city that has been synonymous with the Red Devils for decades.
Should they beat United to secure the title at the Etihad, City will not only inflict humiliation on their rivals, they will also usurp them in the record books by clinching glory with six games to go - that is, one more than Alex Ferguson's 2001 title-winning team.
Guardiola may opt to field a weakened team against Mourinho's side, but his players have been left licking their wounds following a heavy defeat to Liverpool in the Champions League and will no doubt be eager to bounce back with a morale-boosting title-winning performance, which would leave them buoyant ahead of the second leg next week.
The last meeting between the sides took place at Old Trafford in December, with City emerging triumphant with a 2-1 scoreline thanks to a Nicolas Otamendi goal and United will be aiming to stall the celebrations by exacting revenge at Eastlands.
Thoughts of retribution and delaying their rivals from getting their hands on the trophy aside, three points will also serve Mourinho's men well as they endeavour to ensure a second-place finish ahead of Liverpool