Meanwhile, Nemanja Matic also features from the outset for the home side.
They will come up against a familiar face in Javier Hernandez, who makes his return to Old Trafford in West Ham's colours, having arrived from Bayer Leverkusen in the summer.
Joe Hart and Pablo Zabaleta, two members of the Manchester City side Sir Alex Ferguson branded 'noisy neighbours', also feature for the guests.
Manchester United starting XI: De Gea; Valencia, Bailly, Jones, Blind; Matic; Pogba, Mata, Mkhitaryan; Rashford; Lukaku
Subs: Romero, Darmian, Smalling, Fellaini, Herrera, Lingard, Martial
West Ham starting XI: Hart; Zabaleta, Reid, Ogbonna, Masuaku, Noble, Obiang; Fernandes, Arnautovic, Ayew; Chicharito
Subs: Adrian, Byram, Cresswell, Fonte, Collins, Rice, Sakho