The building stands on an isthmus between the Étang de l'Arnel lake and the Mediterranean Sea in the Gulf of Lion, which was once the site of the original city of Maguelone, opposite the present-day town of Villeneuve-lès-Maguelone.

During archaeological excavations in 1967, Roman and Etruscan remains and a number of Visigothic sarcophagi were discovered on this ancient island.

At the fall of the Roman Empire in the 5th century AD, the Visigoths took over part of the region of Melgueil, the island of Maguelone.

[3] Although Maguelone was well protected on the inland side, its strategic position meant that it was very vulnerable to invasions from the sea; in 673, the Visigoth King Wamba was besieged here during his campaign of reconquest of Narbonne.

During the 8th century, the power of the Visigoths weakened and eventually the Kingdom of Toledo collapsed, allowing the Saracens in Spain to increase their attacks on Christian states.

Despite the Muslim invasion, freedom of worship was maintained on the island, its inhabitants being granted the status of dhimmi ("protected person" in Arabic).

Since then the site remained virtually abandoned for three centuries, although it seems that Maguelone continued to support a precarious settlement despite the threat of pirates.

To improve access to the city, which could only be reached by boat, Arnaud built a bridge nearly 1 kilometre (0.62 mi) in length which stretched from the island to Villeneuve-les-Maguelone, which was placed in the charge of a dignitary of the chapter.

The prestige and the increased wealth of the diocese lead to the construction of a new cathedral, replacing the building that dated back to the episcopate of Arnaud.

The archdeacon of Maguelone at this time was Pierre de Castelnau, the papal legate in Languedoc, whose murder in Saint-Gilles in 1208 triggered hostilities against the Cathars.

In the 15th century the bishop moved his residence to Montpellier while the canons remained in Maguelone, managed by the provost of the cathedral chapter.

Sold as national property during the Revolution and classified as a historic monument in 1840, the area of Maguelone was acquired by the historian Frédéric Fabrege in 1852 who began a programme of restoration.