The Roman Emperor Hadrian ordered this building to be constructed as a family mausoleum. He began it in AD 135 and it was finished four years later by his adopted son and successor to the Imperial throne, Antoninus Pius.

The base is 84 metres square in area, and is topped by a 20 metre high drum. The mausoleum was crowned by a statue of the Emperor and a bronze quadriga, and contained urns with the ashes of all the emperors from Hadrian to Septimius Severus (AD 211).

In AD 590 Pope Gregory the Great led a procession against the plague that was decimating the city. As he went past the castle an angel sheathing his sword appeared on top of the mausoleum, which was interpreted as a sign that the plague would end. In thanksgiving the Pope ordered a chapel to be built in the mausoleum, and the placement of a bronze statue of St Michael at the highest point of the building. It was from this that it came to be called the Castle of the Holy Angel (Castel Sant'Angelo).

During the mediaeval conflicts between the Papacy and the Roman nobility, the building was used as a fortress. Pope Nicholas V (1447-1455) built some store rooms at the top of the original construction and added turrets at the corners. The high defensive wall - the Pasetto - built by Leo IV (847-855) joined the castle with the Vatican Palace. Alexander VI (1492-1503) built a passage on top of the wall, so that the Pope could easily reach the fortress in case of siege.

In 1527 Clement VII took refuge there from the troops of the Emperor Charles V, and made several rooms habitable. There were improved by Pope Paul III. After the reunification of Italy a barracks and military prison were placed there.

From the outside the Castle of Sant'Angelo appears as a solid and compact mass: a square plinth at the base reinforced by the corners by the bastions of St Matthew, St John, St Mark and St Luke. The original construction (the mausoleum) can be distinguished from the later additions by the large blocks of travertino and pepperino marble of which it is made.

In the middle, on top of the Roman construction, is the great cylinder wall built by Pope Benedict IX (1033-1044) and completed above by the beautiful curtain-wall of Alexander VI. Above that are the Renaissance papal apartments. At the very top is the terrace, crowned by the bronze statue of St Michael.

The statue has been substituted at least six times. One of the statues in the series ended up being melted down for ammunition during the siege of 1527. The present St Michael dates from 1752, and is the work of the Flemish sculptor Anton Verschaffelt. It replaced a marble statue by Raffaelo da Montelupo, which had stood there from 1544, and is on display in the Cortile dell'Angelo, inside the castle.