The 19-year-old centre-back returns to the heart of los Blancos' defence while Nemanja Vidic does not even make the bench for Sir Alex Ferguson's side for Wednesday's game
The young Frenchman had been struggling with a hamstring injury in recent weeks, but starts tonight ahead of Raul Albiol and Pepe.
Elsewhere Xabi Alonso shakes off a groin injury to start in the deep-lying midfield positions alongside Sami Khedira.
Up front, Karim Benzema is preferred to Gonzalo Higuain, while Diego Lopez continues in goal in the absence of the injured Iker Casillas.
Cristiano Ronaldo, Mesut Ozil and Angel Di Maria make the attacking three that will support Benzema.
For Manchester United, Nemanja Vidic misses out because of injury, with Jonny Evans partnering Rio Ferdinand at centre-back for the English side.
Rafael is handed the task of marking Cristiano Ronaldo, while the Red Devils start with three attacking players in the form of Robin van Persie, Wayne Rooney and Danny Welbeck.
Real Madrid (4-2-3-1): Lopez; Arbeloa, Ramos, Varane, Coentrao; Khedira, Alonso; Di Maria, Ozil, Ronaldo; Benzema
Subs: Adan, Pepe, Carvalho, Essien, Kaka, Modric, Higuain
Manchester United (4-4-2): De Gea; Rafael, Ferdinand, Evans, Evra; Carrick, Jones, Kagawa, Welbeck; Rooney, van Persie
Subs: Lindegaard, Smalling, Valencia, Anderson, Giggs, Cleverley, Hernandez