The villa was built and designed by Pirro Ligorio around 1560 for Cardinal Ippolito II d'Este, son of the Duke of Ferrara, Alfonso I and Lucrezia Borgia, who became governor of Tivoli in 1550.

  

The villa develops around a porticoed courtyard with rooms on two floors decorated by masters such as Federico Zuccaro, Italian Mannerism representant, who worked in the Chapel, in the Hall of Nobility, and in the Hall of Glory. Jerome Muziano  painted the Hall and the Fountain Hall and the stories of Solomon. Cesare Nebbia worked in the First and Second Hall Tiburtina.

The decoration is varied and combines the mythological story related to the legendary founders of Tivoli and to the Sibyl Albunea presence, to the symbols of the Este’ Family (Ercole hero protector of the family, lilies and white eagles are present in the coat of arms) with characters of Old and New Testament such as Noah, Moses and the Virgin Mary.
 
The residence was built in the district called "pleasure seeking Valley", an area of about 4 hectares of artificial different levels on which it was created an Italian garden, embellished with extraordinary  play of water, nymphae rooms, fountains, cascades and little water falls.

  

The visitor today, as in past centuries, walks along ordered paths marked by oak trees, laurel hedges, scented roses and following the sound of water encounters the Hundred Fountains, the Fountain of  Ovato, the Fountain of Bicchierone designed by Gian Lorenzo Bernini, the Fountain of the Dragons, celebrating the visit of Pope Gregory XIII Boncompagni in 1572, in whose family crest is represented  the dragon. The tour ends with the Fountain of Rometta and the magnificent  Fountain of Organ, designed by the French Leclerc and Venard in 1566, a true masterpiece of hydraulic engineering, with a hydraulic organ, recovered after a complex and difficult restoration, that still enchants with its beautiful music.

The originality and beauty of the villa which has enchanted its many guests and visitors along the centuries, including major artists such as Gabriele D'Annunzio and Liszt, in 2001 was recorded by UNESCO as World Heritage Site.