In 1900, Bernard Berenson and Mary Smith Costelloe married and moved to a rural property that had been called "Tatti" or "I Tatti' since at least the Middle Ages. They first rented this property, set in the Settignano foothills east of Florence, from Sir John Temple Leader, a local English expatriate, and then bought from his heir on 10 March 1908. The Berensons employed the English architects Geoffrey Scott and Cecil Pinsent to remodel the house, add a library, and create an Italianate garden set within a working farm. In a short time, they fashioned I Tatti into a comfortable home and center of intellectual, cosmopolitan life, suitably decorated with early Italian panel paintings and Asian art. The Berensons continued to live at I Tatti until they died, Mary in 1945 and Bernard in 1959.
Bernard Berenson, who had graduated from Harvard College in 1887, credited his success as a historian and critic of late Medieval and Renaissance art to his strong education in the humanities. He planned early on to leave his estate to his alma mater and wished to establish a center of scholarship that would advance humanistic learning throughout the world, as well as increase understanding of the values by which civilizations develop and survive. Besides the Villa, his library of some 50,000 volumes, and an archive of photographs particularly strong in Italian Renaissance painting, Berenson left Harvard his works of art, his archive of correspondence and papers, the surrounding farmlands and gardens, and several other buildings. He saw both the collection and the setting at I Tatti as providing encouragement to thoughtful and creative intellectual meditation.