Jose Mourinho has decided to start both of the strikers together as Sergio Ramos, Raphael Varane, Mesut Ozil and Sami Khedira all come into the team
With Benzema and Mesut Ozil coming into the starting line-up, Kaka and Jose Callejon both drop to the bench after starting in the 3-2 Copa del Rey triumph over Malaga on Tuesday.
Elsewhere, Sami Khedira is recalled into the side, coming in for the injured Alvaro Arbeloa with Lassana Diarra reverting to right-back.
Madrid have changed their centre-half partnership for the game with Sergio Ramos returning in place of the suspended Pepe while Raphael Varane comes in for Raul Albiol.
A victory for the home side would open up a six-point lead at the top of the table, with Barcelona not due to play Espanyol until Sunday.
Real Madrid: Casillas, Diarra, Ramos, Varane, Marcelo; Xabi Alonso, Khedira; Ozil, Ronaldo; Higuain, Benzema.
Subs: Adan, Sahin, Kaka, Granero, Altintop, Albiol, Callejon
Granada: Roberto, Nyom, Lopez, Diakhite, Siqueira; Mikel Rico, Yebda; Uche, Martins, Benitez; Ighalo
Subs: Juan, Mainz, Jaime, Geijo, F. Rico, Abel, Cortes