The site is traditionally claimed to have been the place where Publius, the Protos of the island, welcomed and hosted St Paul on the latter’s sojourn to the island in c. A.D. 60; hence, the site’s toponym San Pawl Milqi.

On-site excavations by the Missione Archeological Italiana a Malta between 1963 and 1968 found that the earliest human presence on the site could be dated to the prehistoric Żebbuġ phase (4,100-3,700 BC) through a number of underground burials. Evidence for humans during the Bronze Age’s Borġ in-Nadur phase (1,500-700 BC) is also attested but it remains unclear whether people in this epoch actually used the site or whether the material discovered found its way to San Pawl Milqi from a site up the hill.

The first traces of a farm complex with domestic quarters appear in the 3rd century B.C., betraying Punic cultural influence. The farm complex underwent a series of changes throughout its centuries-long history, including a great fire. Following the fire, the oil-processing installations in the farm complex were refined and the building fortified in Roman imperial period – possibly to withstand any piratic attacks from the nearby coast.

Once abandoned, the whole site was occupied again for agricultural purposes during the Arab period, following which the area occupied by the chapel witnessed the presence of three (if not four) subsequent chapels including the present one built in the beginning of the 17th century.

The longer occupation of the area under the chapel as well as the presence of three subsequent chapels on the same spot form the basis onto which the Missione Italiana sustained their firm belief in the Pauline tradition connected with the site. The origins of this tradition are, however, unclear.