Built on a pre-existing building dating back to the 11th century, Villa I Tatti is at present the headquarters of the Harvard University Center for Italian Renaissance Studies.

After having underwent several transfers of property and experienced a period of decadence, in 1906 the villa, which originally belonged to the Zati family, was bought by the eminent historian and critic of late medieval and Renaissance art, Bernard Berenson. In 1909, Berenson commissioned the renovation of the building and of the garden to the architects Pinsent and Scott (who, a few years later renovated also Villa Le Balze).

When he died, Berenson left the villa, surrounded by a magnificent terraced garden, and his collections of books, photos and art objects to Harvard University, provided that it became a centre dedicated to the study of Italian Renaissance history and art.