The Medici family purchased the villa in the middle of the 16th century. Around 1566-1568, Cosimo I had the complex restructured, and gave it to his son Ferdinando I (first cardinal, and later Grand Duke) who completed the works. The garden in front of the villa, done on a project by Tribolo, develops on three superimposed terraces, created by means of major infill works.

During the restructuring works conducted by Tribolo, the aqueduct structures, which from the springs of Valcenni brought water to La Pietraia, were also redone. Despite these works, the presence of water in the garden was not as impressive as at Castello. Water served exclusively to irrigate the areas of the garden planted with fruit trees and officinal plants.

In the first half of the 19th century, the romantic park was created on a project by Bohemian architect Joseph Frietsch. The function of the park is to connect La Pietraia and Castello by means of an alley, from which depart walks and footpaths, that climb up the hill, skirting brooks and lakes. The park abounds in holm-oaks and cypress trees, and also has several specimens of red oak and various types of pine trees. The sundial on the facade, in part painted and in part carved on a plaster support, still integral and functioning, was made shortly before the mid 18th century. Inhabited until the end of the 19th century, the Petraia complex is today public property and open to visits.

The villa can also be associated with the name of Galileo Galilei. It was precisely from La Pietraia that Lodovico Incontri sent Galileo «two flasks of sour cherry wine from La Pietraia», inviting him to inform His Highness should he desire others. On May 9, 1638, Galileo declared he was willing to visit the Grand Duke who was staying at the villa.