The Red Devils travel to the Etihad Stadium on Sunday afternoon for Ruben Amorim's first derby as manager.
However, Rashford will not be involved for the visitors after he was left out of the matchday squad.
The winger has featured in each of United's 15 Premier League matches so far this season, starting 12 of them.
He also started Thursday's Europa League clash with Viktoria Plzen.
Rashford was replaced by goalscorer Rasmus Hojlund after 56 minutes in United's comeback victory in Czechia.
READ MORE IN FOOTBALL
Forgotten Premier League striker scores from halfway line to snap goal drought
Man City vs Man United live team news: Rashford and Garnacho dropped for derby
The 27-year-old has scored seven goals and provided three assists in 24 appearances so far this term.
However, he has not scored in his last two league appearances, which saw United lose to Arsenal and Nottingham Forest.
Alejandro Garnacho has also been left out of the 18-man matchday squad by Amorim.
The Argentinian played nine minutes off the bench against Plzen and had appeared in each of United's league matches so far this season.
Most read in Football
Championship boss becomes second manager sacked over weekend
Presenter to quit Sky Sports to replace Gary Lineker and become Match of the Day host
Forgotten Premier League striker scores from halfway line to snap goal drought
Ian Holloway restrained by his own players after heated argument with Swindon fan
Garnacho has scored eight goals and added four assists from 24 appearances across all competitions.
talkSPORT understands neither player is injured with Rashford and Garnacho both training this morning.
Asked about his team selection, Amorim told Sky Sports: "We try to evaluate everything training performance, game performances, engagement with teammates, push their teammates up.
"Everything is on the line when we analyse and try to choose the players. It is my selection. Simple.
"I don't want to send a message it is simply an evaluation and they know it. The players are really, really smart. Everybody understands my decision and I have to choose. It is simple selection.
"Of course the context is difficult because we have to win games and we have a difficult situation now. I pay attention to everything, the way you eat, the way you put your clothes to go to a game. Everything. I make my evaluation and then I decide.
"There is a communication after the last training. They are alright. They had training this morning and I was there. They trained really well."
Meanwhile, Hojlund is one of four changes from midweek following his brace off the bench.
Harry Maguire, Mason Mount and Manuel Ugarte also come into the side.
The trio of Joshua Zirkzee, Casemiro and Tyrell Malacia make way as Amorim rotates his side to visit the champions.
All three players have been named amongst the substitutes, though.
A win for United will see them move above Tottenham and into 12th place, although Spurs are in action later in the day.
The Red Devils have not beaten City in the league since January 2023, with their last win at the Etihad a further two years prior.
However, United were victorious in the FA Cup final over their city rivals back in May.
Man City: Ederson, Walker, Dias, Gvardiol, Gundogan, Silva, Doku, De Bruyne, Foden, Matheus Luiz, Haaland.
Subs: Ortega, Stones, Kovacic, Grealish, Savio, Simpson-Pusey, O'Reilly, McAtee, Mubama.
Read More on talkSPORT
Floyd Mayweather releases statement after being attacked and chased by mob in London
Former Everton player Li Tie jailed for 20 years
Man Utd: Onana, de Ligt, Maguire, Martinez, Mazraoui, Ugarte, Fernandes, Dalot, Diallo, Hojlund, Mount.
Subs: Bayindir, Lindelof, Zirkzee, Malacia, Eriksen, Yoro, Casemiro, Antony, Mainoo.