She was the daughter of Cipriano Palafox y Portocarrero, 11th Duke of Peñaranda de Duero, and his wife, María Manuela Kirkpatrick, daughter of the Scottish-born U.S. consul to Málaga and inspiration for Prosper Mérimée's novel Carmen. Her younger sister was Eugenia de Montijo, later wife of Napoleon III of France and empress of the French. While she was a child, her parents moved to France; and on her father's death, her mother moved to Spain with her daughters. She was desperate to get her daughters married off, and Maria and Eugenia became condescendingly known as 'las condesitas' by Madrid society. The Marquis of Alcañices asked his eldest son José Osorio y Silva, Duke of Sesto, to take charge of introducing the sisters to society. He ended up falling in love with Maria - the two remained friends after her marriage. To get closer to her, he became friends with Eugenia - however, she fell in love with him and when she found out that her love was not requited, she attempted suicide with a concoction of phosphorus and milk. As eldest daughter, she acceded to her father's titles, as 12th Duchess of Peñaranda de Duero, 10th Marchioness of Valderrábano, 17th Marchioness of Villanueva del Fresno and Barcarrota, 13th Marchioness of la Algaba, 15th Marchioness of La Bañeza, 15th Marchioness of Mirallo, 14th Marchioness of Valdunquillo, 9th Countess of Montijo, 17th Countess of Miranda del Castañar, 18th Countess of Fuentidueña, 13th Countess of Casarrubios del Monte, 20th Countess of San Esteban de Gormaz, and 18th Viscountess of Palacios de la Valduerna. These titles were incorporated into the House of Alba through her marriage to Jacobo Fitz-James Stuart y Ventimiglia, heir of that house. They married in Madrid on 14 February 1848 and had three children:
She was made a Dame of the Order of Queen Maria Luisa. In 1859 she was diagnosed with tuberculosis, although her symptoms suggest leukemia - her sister Eugenia wanted to get her out of Madrid and so sent her yacht to Alicante. Accompanied by their mother and a doctor, she moved to Paris, where she died on 16 September 1860. Her funeral was held in the Church of the Madeleine and her remains transported to Madrid. There, her friend José Osorio y Silva, by the mayor of Madrid, held a burial ceremony in the Hermitage of Santa María la Antigua, where she had expressed a wish to be buried. Her body was later moved to the family vault of the House of Alba at the Monastery of Inmaculada Concepción, where it remains.
