Jose Mourinho names a strong line-up for the city clash, with Xabi Alonso starting in midfield despite being just one booking away from a suspension
Di Maria suffered a hamstring injury in the 7-1 win over Osasuna on November 6 and was thought to be a doubt for the Clasico against Barcelona on December 10.
But the Argentine has made a quick recovery and starts behind lone striker Karim Benzema, who has been preferred to Gonzalo Higuain, while Cristiano Ronaldo returns after sitting out the 6-2 win over Dinamo Zagreb in the Champions League in midweek.
Lassana Diarra retains his place at right back in the absence of Alvaro Arbeloa, with Sergio Ramos continuing to deputise in central defence for another absentee, Ricardo Carvalho.
Marcelo is fit again, however, and starts at left back instead of Fabio Coentrao.
Atletico, meanwhile, are without star striker Radamel Falcao, who has failed to recover from injury in time for the short trip to the Bernabeu.
In his absence, Adrian starts up front with three attacking players - Diego, Arda Turan and Salvio - just behind the Spanish Under-21 man as both teams begin with the same 4-2-3-1 formation.
There is no start for Jose Antonio Reyes, though, despite the midfielder's impressive performance as a substitute in the 3-2 win over Getafe last weekend.
Atletico hope to secure a first derby win over Real since 1999.
Real Madrid (4-2-3-1): Casillas; Diarra, Pepe, Ramos, Marcelo; Xabi Alonso, Khedira; Di Maria, Ozil, Cristiano Ronaldo; Benzema
Subs: Adan, Coentrao, Albiol, Sahin, Granero, Callejon, Higuain
Atletico Madrid (4-2-3-1): Courtois; Perea, Godin, Dominguez, Filipe Luis; Assuncao, Gabi; Arda Turan, Diego, Salvio; Adrian
Subs: Asenjo, Suarez, Juanfran, Pizzi, Reyes, Koke, Miranda