The strike duo have been struggling with injuries since the international break, but Louis van Gaal has thrown both of them back into the starting XI as he makes four changes to the side that won 2-1 at Watford on Saturday.
Alongside Rooney and Martial, Matteo Darmian and Marcos Rojo have been reinstated to the back four. Ashley Young and Juan Mata are back among the substitutes, while Phil Jones and Ander Herrera have not been included in the squad after picking up injuries at the weekend.
Meanwhile, PSV have made two changes to their side as they seek their third Group B victory.
Man Utd starting XI: De Gea; Darmian, Smalling, Rojo, Blind; Schweinsteiger, Schneiderlin; Lingard, Rooney, Memphis; Martial
Subs: Romero, McNair, Young, Fellaini, Mata, Pereira, Wilson
© Getty Images
PSV starting XI: Zoet; Arias, Moreno, Bruma, Brenet; Propper, Guardado, Hendrix; Narsingh, De Jong, Locadia
Subs: Pasveer, Isimat-Mirin, Pereiro, Schaars, Maher, Poulsen, Bergwijn
Follow every minute of the game from Old Trafford in Sports Mole's live text commentary here.