Pep Guardiola's side have opened an eight-point gap at the top of the table after just 15 games and remain unbeaten going into this weekend's meeting at Old Trafford.
Should City claim a victory against Jose Mourinho's men it would blow a major hole in their neighbours' chances of claiming the title, despite it still being relatively early in the campaign.
City have now won 13 successive league matches – a joint-record within a single top-flight season - while United are unbeaten in their last 40 home games in all competitions, a record of their own.
The game is the biggest of the season so far, but which players available for selection from each side would make a combined XI judged on their form so far this season? Goal takes a shot at picking the team...
DAVID DE GEA (United) - As impressive as City goalkeeper Ederson has been this term, David De Gea's show-stopping performance during the Red Devils' 3-1 victory at Arsenal last time out made it impossible to overlook the Spain international. De Gea made an incredible 14 saves at the Emirates and is arguably the form 'keeper in Europe at present.
ANTONIO VALENCIA (United) - The full-back areas were the most difficult to fill, with the right-back spot a straight battle between Valencia and Kyle Walker. The United defender was outstanding at Arsenal last weekend and followed it up with another solid performance in the Champions League in United's 2-1 win at home to CSKA Moscow.
NICOLAS OTAMENDI (City) - While it is United players who dominate the back five of our combined XI, Otamendi's inclusion is fully deserved. The City centre-back's partnership with John Stones, who misses the game with a hamstring injury, has been the basis of a solid defence for Guardiola this term.
MARCOS ROJO (United) - Mourinho has ruled Eric Bailly out of the game, while Phil Jones is a major doubt. With Stones also unavailable, Marcos Rojo claims the second centre-back slot in our four-man backline having been rested in the week.
ASHLEY YOUNG (United) - The inclusion of Young at left-back is a result of both Benjamin Mendy's absence and Luke Shaw's exile, though the latter returned to the United starting XI against CSKA. Young's stint in the left wing-back role has been a successful one, similarly to that of Fabian Delph's in the same position at City.
KEVIN DE BRUYNE (City) - Undoubtedly one of the performers of the season across Europe so far this season, De Bruyne's selection comes as no surprise. The Belgian playmaker has scored four goals and assisted eight while averaging over three key passes per league outing.
NEMANJA MATIC (United) - While the defensive positions are stacked with the red of United, the front two thirds of the team is top-heavy with City stars. Every attack requires a pivot, though, and with Paul Pogba missing out on Sunday's game through suspension, it is up to Matic to govern the central spot in midfield.
DAVID SILVA (City) - Guardiola is unsure regarding the availability of Silva ahead of the tie but if he is passed fit then he will almost certainly be selected in City's XI. The 31-year-old's importance to the club has again been highlighted this season and his two goals and eight assists in 14 starts is a very sturdy return.
RAHEEM STERLING (City) - Ten starts for the England international so far this season, nine goals. Sterling has blossomed under the tutelage of Guardiola and has proved himself as a consistent match-winner across the campaign. The 22-year-old gets into the team ahead of the likes of Marcus Rashford, Anthony Martial and Henrikh Mkhitaryan.
SERGIO AGUERO (City) - To choose a single forward from Romelu Lukaku, Zlatan Ibrahimovic, Gabriel Jesus and Sergio Aguero is difficult, though it is the latter who gets the nod in our combined XI following his nine goals this term. Jesus was a close second having been directly involved in 21 goals in his 24 Premier League appearances so far in his career (15 goals, six assists).
LEROY SANE (City) - A slow start to life in Manchester has been followed by an outstanding season this time around, with Sane's displays on the left of the attack a crucial part of City's success. The 21-year-old has so far claimed six goals and six assists from 14 appearances in the top flight this season.
And here's how they line up! Disagree with our selection? Who would make your combined XI?