It is located about 35 kilometres (22 mi) south of Grosseto, on the Lagoon of Orbetello, which is home to an important Natural Reserve.

Orbetello was an ancient Etruscan settlement, which in 280 BC passed under the control of the Romans, who had founded their colony of Cosa (near the modern Ansedonia).

The emperor Domitian had a substantial property here, which had belonged to the Domitii Ahenobarbi and he inherited through his wife Domitia Longina.

This led to the inconclusive naval Battle of Orbetello on 14 June; in July, a Spanish army forced the French to lift the siege.

In 1713 this district passed by treaty to the emperor, in 1736 to the king of the two Sicilies, in 1801 to the kingdom of Etruria, and in 1814 to the Grand Duchy of Tuscany.