Although an episcopal see of Alessano (Alexanum in Latin) was probably established under Norman rule in the 10th or 11th century, the regular succession of its bishops began only in 1283 with a Giovanni from Naples. Until the 16th century, papal bulls regarding the bishopric called it either Alexanum or Leuca. It was a suffragan of Otranto. For three years (1518–1521), it was united with the diocese of Lecce under Bishop Giovanni Antonio Acquaviva d'Aragona. Byzantine usages continued to be observed until abolished by Bishop Ercole Lamia (1578-1591).
The existence of the residential see was ended by the bull De utiliori of 27 June 1818 of Pope Pius VII, which assigned its territory to the diocese of Ugento. As a result, the bishopric of Alexanum is today listed by the Catholic Church as a titular see.