The Catholic Monarchs, Isabella I of Castile and Ferdinand II of Aragon created the title and awarded it to Luis de la Cerda y de la Vega on October 31, 1479.
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He married Juana Manuel de Portugal (ca. 1520-1568), daughter of Sancho I de Noronha Portugal, 2nd Count of Faro on 7 April 1541, at Ocaña.
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In 1368, Bernal de Foix, the first Count of Medinaceli, took the side of the royal bastard Enrique II of Castile against his legitimate brother, King Peter of Castile.
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It was copied during the second half of the 16th century and kept at the library of the Duke of Medinaceli's house, hence its name.
He belongs to one of the most important families of Spain, the House of Medinaceli, being grandson of Victoria Eugenia Fernández de Córdoba, 18th Duchess of Medinaceli, and is a descendant of King Ferdinand I of Aragon.