Charting the life of Isabella I of Castile, one of the most important women in Spain’s history, Isabel follows her passionate story from childhood to being crowned Queen. From her political struggles within King Henry IV's court to her wedding to Ferdinand of Aragon, the drama encapsulates the passions, emotions and sacrifices of a woman who refused to just be a figurehead and whose outlook was ahead of her time.

As the life of Charles of Habsburg is told since his arrival to Spain, it can be seen how the heir to the crowns of Germany, Burgundy, the Netherlands, the Free County, Artois, Nevers and Rethel, of the territories of the Crown of Aragon and its related Italian territories, and of the territories of the Catholic Monarchs in Castile, North Africa and the Americas, matures as a statesman and gets stronger in face of menaces around him and good and bad advice from his counselors.