Castro derives its name from Castrum Minervae (Latin for "Minerva's castle"), which was an ancient town of the Sallentini, about 15 kilometres (9 mi) south of Hydruntum. Its ancient temple of Minerva was said to have been founded by Idomeneus, who formed the tribe of the Sallentini from a mixture of Cretans, Illyrians and Italian Locrians.
It is also said to have been the place where Aeneas first landed in Italy, the port of which he named Portus Veneris ("Port of Venus"). The temple had lost some of its importance in Strabo's day.
The bishopric of Castro was founded by Pope Leo II in 682. In the 9th century it is mentioned as a suffragan of Santa Severina, but in the 12th century it came under the jurisdiction of Otranto. In the 16th century Castro was destroyed by the Turks and the bishop moved his residence to Poggiardo in 1572. The territory of the diocese was added to that of Otranto in 1818, and Castro di Puglia, no longer being a residential bishopric, is today listed by the Catholic Church as a titular see.