She adopted her stage name in tribute to the legendary French courtesan Ninon de l'Enclos and began to work in the chorus of the Cuban comedians Mimí Cal and Leopoldo Fernández, respectively known as "Nananina" and "Tres Patines".

Although from the beginning Sevilla was marked by the eccentricity of her hairdos and gowns, it was director Alberto Gout who established her as one of the ultimate erotic figures of Mexican cinema, leading her in legendary films as Aventurera (1949), and Sensualidad (1950).

In 1955, the future French director François Truffaut made a review of Llévame en tus brazos, in which he wrote: "Is Ninón dancing for glory?

With the decline of the Golden Age of Mexican cinema, Ninón Sevilla retired from the industry, but returned in 1981 by the hand of Mario Hernández, who directed her in the 1981 film Noche de Carnaval, for which she received the Silver Ariel Award for Best Actress of the Year.

In 2014, Ninon Sevilla was the subject of tributes from the Mexican Academy of Film Arts and Sciences and the Cineteca of Mexico for her career and influence in their national cinema.