Duke of Medinaceli (pronounced: [meðinaˈθeli]) is a title of Spanish nobility. 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 31 October 1479. Luis also held the title of 5th Count of Medinaceli, which title was first awarded in 1368 to his ancestor, Bernal de Foix.
In 1368, the King of the Crown of Castile bestowed the title "Count of Medinaceli" on Bernal de Foix, the second husband of Isabel de la Cerda. Their grandson Luis, 3rd Count of Medinaceli, eventually inherited the title and changed his family name to "de la Cerda." Later on, Queen Isabella I of Castile raised the title from Count to Duke in 1479 for Luis de la Cerda y de la Vega, 5th Count of Medinaceli.
Luis de la Cerda y de la Vega, 1st Duke of Medinaceli (c. 1442–1501), Count in 1454 and Duke in 1479, was the first person awarded the title of "Duke of Medinaceli". He fought in battles against Portugal and the Moorish Kingdom of Granada.
Duke Juan I de la Cerda y Vique, the 2nd Duke of Medinaceli, was a bastard who was legitimated with Grandee by the Spanish Crown in 1520. He was a courtier under Queen Isabella I of Castile, her daughter Queen Joanna of Castile, and her son King Charles I of Spain. He took part in the battles for the "incorporation" of the Kingdom of Navarre on behalf of Ferdinand II of Aragon, the grandfather of King Charles I of Spain.