The £89.5 million midfielder suffered a thigh injury in training on Friday and was ruled out after a late check by United's medical staff on Saturday morning.
And while Martial also sits out due to the same muscle injury which saw him miss the trip to Crystal Palace on Monday, Marcus Rashford makes his first start in 10 league matches in the forward line.
Marouane Fellaini is back in the squad after injury but has to be happy with a place on the substitutes' bench. He is joined by Jesse Lingard, with Juan Mata starting in his stead on the right of the attacking midfield line.
For Liverpool Jordan Henderson is on the bench, with Emre Can, James Milner and Alex Oxlade-Chamberlain in the three midfield positions.
Up front, Mohamed Salah returns alongside Sadio Mane and Roberto Firmino.
The winners of today's game will take second place in the Premier League table, with a draw enough to keep United ahead of Liverpool in the standings.
Man Utd XI: De Gea, Valencia, Bailly, Smalling, Young, McTominay, Matic, Mata, Sanchez, Rashford, Lukaku.
Subs: Romero, Darmian, Lindelof, Shaw, Carrick, Lingard, Fellaini.
Liverpool XI: Karius, Alexander-Arnold, Lovren, Van Dijk, Robertson, Can, Milner, Oxlade-Chamberlain, Salah, Mane, Firmino.
Subs: Mignolet, Gomez, Matip, Henderson, Wijnaldum, Lallana, Solanke