The original core of the works of the Vatican Museums is formed of the collection of sculptures that were exhibited in the "Court of the Statues", nowadays called "Cortile Ottagono", on the desire of Giulio II Pope from 1503 to 1513 after Christ.

Clement XIV and Pio VI fitted out the first collections of the Pontificate Museums and Galleries, while Pio VII enriched the Epigraphic Collection and increased the rooms dedicated to the Classical Antiquities, adding the "Chiaramonti Museum" with the rooms of the Hall, of the Lapidaria Gallery and of the "Braccio Nuovo" (New Arm) where are hosted a series of statues, busts, sarcophagus and figures in relief with more than 5000 pagan and Christian inscriptions, and some of the most famous works of the Antiquity such as the statue of "Augusto di Prima Porta", the colossal statue of the Nile and the "Doriforo".
Gregorio XVI founded the Etruscan Museum and the Egyptian Museum, to collect the works coming from the excavations and explorations made in Etruria and in Egypt.
The actual organisation of the Vatican Museums is due to the wish of Pio IX and Pio X, who added respectively the Christian Museum and the Hebraic Lapidary formed with the inscriptions and sculptures coming from the Hebraic and Christian cemeteries of Rome. Are also part of the rooms of the Vatican Museums:

• The Gallery of the Tapestries, fitted out since 1814 after Christ in the decorated rooms during the Pontificate of Pope Pio VI.
• The Gallery of the Geographic Maps with the painted maps on the walls in forty frames, decorated under Gregorio XIII and restored during the Pontificate of Urbano VIII.
• The Sobieski Room, so called from the painting of Giovanni III Sobieski, king of Poland, which makes busy an entire wall.
• The Room of the Immaculate, located in the Borgia Towers, containing frescoes relatives to the dogma of the Immaculate Conception.
• The Rooms of Raffaello, which name is due to the frescoes realised by Raffaello in four rooms belonging to the antique residence of Giulio II.
• The Sixtin Chapel that takes its name from its founder Sisto IV and welcomes the very famous frescoes of Michelangelo on the vault and on the back walls with the "Universal Judgement".
• The Borgia Apartment, founded by Pope Alessandro IV Borgia, and decorated by the frescoes of Pinturicchio inspired by the classical world and the Roman mythology.
• The Vatican Picture-Gallery, located by Pio XI in 1932 after Christ in an apposite building in the new entrance of the Museums.
• The Missionary-Ethnological Museum founded by Pio XI, initially placed in the superior floors of the Lateranense Palace and then moved, on the desire of Giovanni XXIII, in the same building where are also exhibited the collections ex-Lateranensi.
• The Collection of Modern and Contemporaneous Religious Art, wanted by Paolo VI and the Pavilion of the Coaches fitted out in 1973 in the rooms extracted from the Square Garden.