Her paternal grandparents were the famous condottiere Giovanni delle Bande Nere and Maria Salviati (granddaughter of Lorenzo the Magnificent).

[2] Her maternal grandparents were Pedro Álvarez de Toledo, Viceroy of Naples, and Maria Osorio, 2nd Marchioness of Villafranca del Bierzo.

[4] Like all children of the Medici ducal couple, Lucrezia received a good education and was brought up in strict accordance with Spanish court ceremonial, which her mother followed.

[5] In 1557, as a sign of reconciliation between Ercole II d'Este, Duke of Ferrara (who held a pro-French position), and King Philip II of Spain, it was decided that Alfonso d'Este, Hereditary Prince of Ferrara, would marry Maria de' Medici, the eldest daughter of Cosimo I, an ally of Spain.

King Henry II of France's sister, Margaret, and daughter, Elisabeth, were suggested instead to the Ferrarese court as wives for the hereditary Prince.

On 3 July, 24-year-old Alfonso and 13-year-old Lucrezia were married in the chapel in the Palazzo Pitti[8] (or according to another version in the Basilica of Santa Maria Novella[9]), by the bishop of Cortona, Giovan Battista di Simone Ricasoli.

At the request of his mother-in-law, the hereditary Prince of Ferrara agreed to postpone the wedding night until such time as his bride reached sexual maturity.

[a][1][10] Together with her sister Isabella, the new hereditary Princess of Ferrara continued to live in the chambers of the Palazzo Pitti, isolated from the rest of the world.

Less than a year after her arrival, on 21 April 1561, she died, after suffering a month of fever, severe weight loss, constant coughing and a permanently bleeding nose.

[12] According to Dr. Andrea Pascvali, sent from Florence to the Duchess by her father, Alfonso was concerned about Lucrezia's state of health during the entire period of her illness.

An autopsy by the same doctor revealed that the Duchess had died of "putrid fever"; modern historians believe that her death was caused by pulmonary tuberculosis.