The promontory was probably already inhabited by the Etruscans, whose presence in the surrounding Maremma is widely documented by archaeological remains. The history of Monte Argentario is, however, better known when the Etruscan Etrurian guide replaces the Roman one and the whole area became part of the personal property of the Domizi Enobarbi family who obtained it as compensation for the sums they had lent to the Roman republic. during the Second Punic War, until under the control of the Roman Church in the 4th century. In the Middle Ages, also as a result of the less traffic that took place on the Via Aurelia and the gradual swamping of the Maremma, these places remained for a long time little inhabited.
In the late Middle Ages the mountain followed the fate of Orbetello, passed under the possessions of the Aldobrandeschi, Orsini, Ladislao, king of Naples and Siena, to end then under the rule of the Spaniards around the middle of the sixteenth century. At this time date back the buildings and fortifications that Philip II had built to defend the promontory and the surrounding lands from possible Turkish attacks, making the defensive pivot of the State of the Presidii and reactivating the civil life of these places. The Spaniards built on the promontory and along the entire coast between Talamone and Ansedonia, a series of fortresses and watchtowers, among them, the Spanish Fortress in Porto Santo Stefano and Forte Filippo, Forte Stella and the Rocca aldobrandesca in Porto Ercole. The Spanish domination lasted until 1714 and the Argentario ended under the control of the Austrians until 1738 and then passed under the rule of the Bourbons of Naples until the Napoleonic period. Defeated Napoleone, in 1815 the Spanish possessions passed to the Grand Duchy of Tuscany until 1860, when they were annexed to the Kingdom of Italy. Historical fact was the stop of Garibaldi and the Thousand on May 9, 1860 in Porto Santo Stefano, during the transfer journey from Quarto to Marsala.
During the last world war, Porto Santo Stefano was a very important logistic base for the Germans, for this reason Monte Argentario was the scene of violent bombardments, the inhabited centers were hard hit by the allies suffering the loss of many civilians. The episode was emphasized by Radio London, as the success of the next winners of the conflict on the area that at the time constituted the true stronghold of the Wehrmacht in Italy. The bombardments made Monte Argentario the second most common in Italy, destroyed by the raids of Anglo-American areas, after Cassino, in the Second World War.
In 1971 in Monte Argentario the Tuscan Virus was isolated for the first time in some phlebotomies.
