Sant'Antioco is the second largest island of the region Sardinia, after Sardinia itself, with a surface of 109 km2; it is also the fourth in Italy after Sicily, Sardinia itself and Elba. It is located some 87 km from Cagliari, to which is connected through the SS126 state road, using a modern bridge. The island is divided between the two municipalities of Sant'Antioco and Calasetta. Other settlements are the small tourist resort of Maladroxia (a frazione of Sant'Antioco municipality) and Cussorgia, part of Calasetta.

The island of Sant'Antioco was settled at least from the 5th millennium BC (the so-called culture of San Michele of Ozieri), which based mainly on fishing and agriculture. Typical tombs (called domus de janas) and menhirs belonging to this culture have been found. The island also housed nuraghe civilizations: findings include the nuraghe of Su Niu de Su Crobu ("Crow's Nest").

The city of Sant'Antioco was founded in the 8th century BC by the Phoenician, with the name of Solki, of which a tophet (children) necropolis has been excavated. Later (6th century BC) it became a Carthaginian colony, to which another necropolis belongs. The Punic domination ended in the 2nd century BC, when Solki was conquered by the Romans, who connected it to the mainland through an artificial isthmus. During the civil war between Julius Caesar and Pompey it sided for the latter, being severely punished after his defeat. During Roman times, it was called Plumbaria, after its lead deposits.

The current city name derives from St. Antiochus, evangelizer of the area, who was martyred in 125 AD. After the decline and the end of the Western Roman Empire, Sant'Antioco was a fortified strongpoint of the Byzantines. It was repeatdely attacked by the Saracens starting from the early 8th century, and gradually abandoned by the inhabitants, who fled in the more proteced inner area, the island remaining mainly the end of pilgrimages of Antiochus' devoted. A new settlements (bidda in Sardinian) was established around 935 by the judge (the local title for lord) of Cagliari, but this also was abandoned after the end of the giudicato. The island was a territory of the Kingdom of Sardinia (created in 1354) and later was acquired by archbishopric of Cagliari (1503) and, in 1758, by the religious Order of SS. Maurizio and Lazzaro: at the time it had 38 houses, 15 workshops, 164 huts, with some 450 inhabitants.

In January-May 1793 the island was occupied by French troops under admiral Laurent Jean François Truguet, and the citizen freed from ecclestiastical taxes. The last attack from North African pirates occurred in 1815 (the same year in which the relics of the patron saint were brought back to the cathedral).

• The Palaeo-Christian Basilica of Sant'Antioco, restored in 1089-1102

• Roman bridge

• Ancient akropolis

• Phoenician and Punic necropolises

• Ferruccio Barreca Archaeological Museum

• The Forte Su Pisu (1812)

• Byssus museum

In the period from 15 May to 15 June a famous Tuna "mattanza" is held, with fishing of Northern Bluefin Tuna (Thunnus Thynnus).