Edinson Cavani, suspended for three games after being charged by the FA over a controversial social media post, is among those missing out while Alex Telles, Nemanja Matic, Mason Greenwood also dropped to the bench.
Scott McTominay, Fred, Anthony Martial and Luke Shaw have all returned to the starting XI.
Tyrone Mings returns to the heart of the Villa defence, with Kortney Hause dropping to the bench. Villa are otherwise unchanged from a 1-1 draw with Chelsea.
That seems unlikely. Dean Smith’s side have one of the meanest defences in the Premier League, having conceded only 14 goals in their first 14 matches.
Manchester United vs Aston Villa team news
Man Utd XI: De Gea, Bailly, Maguire, Pogba, Martial, Rashford, Fred, Fernandes, Shaw, Wan-Bissaka, McTominay
Aston Villa XI: Martinez, Cash, Konsa, Mings, Targett, Douglas Luiz, McGinn, El Ghazi, Grealish, Traore, Watkins
Only Manchester City (9) have conceded fewer. Manchester United, by comparison, have let in 23 in their 15 league matches.
Aston Villa are flying high in the Premier League and could move a point behind United, with a game in hand, if they take the three points.
They have only taken three points against United once in the last 43 attempts.
United are unbeaten in their past nine matches, while Villa have not tasted defeat in their last five.