- Great-niece of Spanish sculptor Victorio Macho (1887-1966).
- Daughter of Ramón Macho Calvo, a patternmaker of footwear whose family hailed from Palencia.
- Her paternal grandfather, Castor Macho Galindo, was born in Herrera de Valdecañas, Province of Palencia. Her paternal grandmother, Benedicta Calvo Burgos, was born in Magán, Province of Toledo.
- She thought María Fernanda, la Jerezana (1947) and Currito de la Cruz (1949) were her most important movies.
- She was first known as Natividad Macho (her birth name). Shortly after her debut, she decided to choose a different name. Rafael de León, the famous Spanish lyricist, suggested the names Nati Madrid, Nati Sevilla, or Nati Córdoba, but Nati's mother chose "Mistral" (an Occitan word that means "masterly").
- Was the first actress to play the Dulcinea role in the Spanish version of the Broadway musical Man of La Mancha (El hombre de La Mancha). Two numbers, "Un sueño imposible" and "Dulcinea", became an integral part of her repertoire and she recorded and performed them many times throughout her long career.
- In her live performances, she frequently included the patriotic Spanish song "De España vengo" ("I Come From Spain") from the 1918 zarzuela El niño judío (The Jewish Boy). She recorded the song in Mexico in 1973 and opened her episode of Cantares (1978) with it.
- Discovered the famous Spanish guitar duo Los Gemelos ("The Twins") and recorded an extended play with them (the first of several collaborations) in 1965. María Dolores Pradera also began recording with Los Gemelos that same year and they eventually became Pradera's frequent (and almost exclusive) accompanists. Mistral later remarked, "María Dolores took them from me".
- Early in her career, she toured Europe for five years and performed in Berlin, London, Brussels, Hamburg, Paris, Amsterdam, Stockholm, and Copenhagen.
- Her first great success on the Spanish stage was her stellar performance in Luis Escobar's Te espero en el Eslava (1957), a revue set in Madrid's Teatro Eslava. She made a name for herself as a dramatic actress with her portrayal of the main character in José Tamayo's production of Ramón del Valle-Inclán's play Divinas palabras (1961).
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