Grand Duke Ferdinando I de' Medici commissioned the impressive villa from Bernardo Buontalenti. It became known also with the name of "La Ferdinanda" or "Villa of the One Hundred Chimneys" for the picturesque series of chimneys of various shapes that rise from its roof. Intended as a hunting lodge, the villa often hosted the grand-ducal court. Inside, the hall called "of the villas" housed the seventeen lunettes (today conserved in the Museum of "Florence as it was") depicting the Medici residences that Flemish artist Giusto Utens painted in the late 16th century. It was then that the villa with its iconographic collection became the ideal centre of the Medici possessions in the Florentine countryside.

The villa too, is a "Galilean site": from June 24 to August 23, 1608, the court was staying at Artimino, and Grand Duke Ferdinando I de' Medici invited Galileo Galilei to come in August to instruct his son (the future Grand Duke Cosimo II) in mathematics. The villa was also theatre of many experiments by the Accademia del Cimento. In September 1657, numerous endeavours were made to measure atmospheric humidity under different meteorological conditions, utilising the condensation hygrometer. Moreover, the academicians performed barometric experiments in the surrounding countryside in order to verify the variation of atmospheric pressure with changes of altitude.