Cruz first achieved fame when she appeared in the Lucio Villalba-directed video clip La fuerza del destino for the Spanish synthpop group Mecano. She later started a relationship with Nacho Cano, a member of the group. A TV presenter for the teen-oriented program La Quinta Marcha, she also had early exposure in Série Rose, a French erotic TV serial. In one episode she played the role of a blind prostitute and in another played a young noble woman pretending to be a young nobleman in a comedy of errors. She also directed Nacho Cano's video of "El waltz de los locos", in 1994.

Cruz's first major films were Jamón, jamón and Belle Époque, a film which won an Academy Award for Foreign Language Film. In 1997, she starred as Sofía Pangia, alongside Eduardo Noriega in Abre los ojos, directed by Alejandro Amenábar, while in 1999 she appeared in Pedro Almodóvar's Todo sobre mi madre (All About My Mother), which won an Academy Award for Foreign Language Film. In 2000 she appeared