The 46-year-old actor will portray the notorious Colombian drug lord, with Cruz as Escobar's real-life former lover, Virginia Vallejo. The movie is based on Vallejo's memoir Loving Pablo, Hating Escobar.
Escobar will follow the drug trafficker's rise to power and romantic relationship with Vallejo. Escobar died in a shootout with police at age 44 in 1993, and Vallejo later sought asylum in the U.S. after testifying against the criminal's associates.
Fernando Leon de Aranoa (Mondays in the Sun) will adapt and direct the film, with Bardem, Dean Nichols and Christophe Lambert as producers. EuropaCorp is shopping the movie to distributors at the 2015 Cannes Film Festival.
Bardem and Cruz married in July 2010, and have two children, four-year-old son Leonardo and one-year-old daughter Luna. The couple previously collaborated on such films as Jamon Jamon, Vicky Cristina Barcelona and The Counselor.