The two English giants currently occupy the top two spots in the Premier League table, but Man City can be considered the champions-elect, while Man United's bid for glory looks all but over as a 14-point chasm separates them from Pep Guardiola's ruthless charges.
The Red Devils endured a midweek outing to forget as they played out a drab 0-0 draw with Crystal Palace at Selhurst Park, and Ole Gunnar Solskjaer's side surely must focus on their top-four place rather than an unlikely title charge.
In contrast, record-breaking City marched to their 21st win in succession with a 4-1 victory over Wolverhampton Wanderers on Tuesday evening - a result which leaves them six off The New Saints' all-time record of 27 consecutive triumphs - and it would take a catastrophe for Guardiola's side to lose their grip on the crown now.
Both Man City and Man United will be able to call upon most of their first-team regulars for this clash, and with that in mind, Sports Mole picks a combined XI from both squads, using only players expected to be available for the showdown.
With David de Gea confirmed to be missing Sunday's derby after the birth of his child, there was only ever one contender for the number one spot in this team. Ederson has marshalled a City backline which has shipped just 17 league goals all season - 16 when he has been on the pitch - and the Brazilian goalkeeper has already kept 15 clean sheets in the top-flight this term, unsurprisingly a league high. Dean Henderson has big gloves to fill this weekend in the absence of De Gea, but the Spaniard would have struggled to displace Ederson either way.
It seems laughable to select Joao Cancelo at right-back when he could easily occupy a multitude of positions with the same panache - such is the unbridled freedom he is granted in Guardiola's system. The former Juventus man has consigned his difficult start to life at the Etihad to history and is enjoying his football more than ever - with one goal and two assists in the league to boot - and he keeps Aaron Wan-Bissaka and Kyle Walker out of the team. There is one United representative in the back four, though, as Luke Shaw continues to restrict Alex Telles and Brandon Williams to substitute appearances in the United XI with hugely improved performances this term, with the Englishman and his five assists earning a spot in our team over Oleksandr Zinchenko and the forgotten man Benjamin Mendy.
With only four goals let in during the 17 matches they have played together in the Premier League, the centre-backs pick themselves in this team. Ruben Dias has taken no time at all to announce himself as a leading defender in the English top flight and has made the most passes out of any player so far this season (2,046 - 15 more than second-placed teammate Rodri), and with 93.4% of those being accurate, he walks into our XI. Dias's teammate John Stones has popped up with three strikes at the correct end of the pitch and is enjoying a revival that not many fans could have predicted at the start of the season, so he gets the nod over United trio Harry Maguire, Eric Bailly and Victor Lindelof - the latter of whom is struggling with a back problem.
Guardiola has insisted that he will still be able to get the best out of Ilkay Gundogan even after Kevin De Bruyne's return from injury, and the former Borussia Dortmund man is sure to be reluctant to drop deeper given his recent ruthlessness in front of goal. Gundogan's contributions have slowed down a bit in the past couple of weeks, but with 11 goals struck in the Premier League this term, there was no leaving him out. Even though De Bruyne has missed a portion of the campaign, no player has provided more assists than his 11 so far, so he joins Gundogan in the midfield ahead of City teammates Rodri, Bernardo Silva and Phil Foden, all of whom were worthy candidates.
City players unsurprisingly dominate our combined XI, but it would have been criminal to overlook Bruno Fernandes. The former Sporting Lisbon man continues to be criticised for a perceived ineffectiveness in crunch matches - only one of his 26 goals or assists in the league so far has come against a 'Big Six' team - but United would struggle to maintain a top-four charge without their inspirational playmaker and he was a routine pick. The Red Devils have a trio of midfielders in Paul Pogba, Donny van de Beek and Juan Mata either injured or doubtful for this game, but even the former would have trouble earning a spot in this star-studded midfield on a good day.
Normally a left-winger by trade, Raheem Sterling is just as capable of proving a threat on the right-hand side of the attack and has been another integral cog in Guardiola's system this season. It is notoriously difficult to nail down a regular spot in City's attacking trident, but Sterling has started 22 of his side's 27 league games this term and has registered nine goals and six assists in that time, so he gets the nod over Riyad Mahrez and Ferran Torres.
The final United representative of our lineup is Marcus Rashford, whose work off the pitch continues to make as many headlines as his footballing endeavours, and while he has not been as clinical in the second half of the campaign, the nine goals and eight assists he has already chalked up in the top flight earns him a place in the attack over Mason Greenwood and Anthony Martial - the latter of whom is doubtful with a knee problem anyway.
In what may very well be his farewell season at the Etihad, Sergio Aguero has not had a campaign to remember. The injury and coronavirus-stricken Argentine is yet to find the back of the net in the Premier League having been restricted to a meagre six appearances, but as he is now back in action, Aguero will be desperate to finally get off the mark for the campaign and increase his impressive tally against Man United this weekend. Only Wayne Rooney (11) has struck more goals in the Manchester derby than Aguero (9), and if this season does turn out to be his last in sky blue, hitting double figures against City's bitter rivals would certainly be a fitting way to say goodbye.
Watch the Sports Mole Football Shorts prediction for this game below: