He was the son of Don Luis de la Cerda, 1st Duke of Medinaceli by third wife Catalina Bique de Orejón.
Since his parents only married In Articulo Mortis in 1501, he was considered a bastard for the first half of his life but was legitimated by the Catholic Monarchs as the eldest surviving male issue from the first Duke.
He took part in the battles for the incorporation of the Kingdom of Navarre into the unified Kingdom of Spain on behalf of King Ferdinand II of Aragon.
He also was a courtier under Queen Isabella I of Castile till 1504, of her daughter Queen Joanna of Castile The Mad, and later supported her son King Charles I since 1516.
In 1512, he married for a second time, with María de Silva (1494 – 16 August 1544), daughter of Don Juan de Silva, 3rd Count of Cifuentes]with whom he had four more children.