The forward has recovered from a hamstring problem after undergoing horse placenta treatment in Belgrade, while Cristiano Ronaldo and Karim Benzema are fit for Los Blancos
The Spain international appeared to have no chance of featuring in Lisbon after suffering a hamstring injury in last weekend's Liga title decider at Barcelona.
However, Costa traveled to Belgrade during the week to undergo a revolutionary treatment involving horse placenta and has now been given the all-clear to start up front alongside David Villa.
Madrid, meanwhile, has been boosted by the availability of star striker Cristiano Ronaldo, who had been struggling with a thigh problem.
In addition, the Portugal international will be joined in Carlo Ancelotti's starting lineup by Karim Benzema, who has recovered from a hamstring injury.
However, Pepe has been ruled out with a calf problem and will be replaced at the heart of the Madrid defense alongside Sergio Ramos by Raphael Varane.
Elsewhere, Sami Khedira, who only recently returned from a knee injury, takes over from the suspended Xavi Alonso in midfield.
Atletico Madrid: Courtois; Juanfran, Miranda, Godin, Filipe; Gabi, Tiago, Koke, Raul Garcia; Villa, Diego Costa.
Real Madrid: Casillas; Carvajal, Varane, Sergio Ramos, Coentrao; Khedira, Modric, Di Maria; Cristiano Ronaldo, Benzema, Bale.