The Sanseverino family originates from the Norman knight Turgisio of Arnes, an alleged descendant of the House of Normandy, who was invested with the county of Rota by Robert Guiscard in 1061.

The name Sanseverino originates from the castle in Mercato San Severino which Turgisio adopted as his surname.

In the struggle between the Aragonese and the Angevins for the throne of Naples, the family was divided: Roberto Sanseverino d'Aragona, count of Caiazzo (d. 1487), supported Ferdinand I of Naples, but his son Galeazzo (d. 1525), who was married to a daughter of Ludovico Sforza, died fighting for the French at the battle of Pavia.

The condottiere Ferdinando Sanseverino, Prince of Salerno (d. 1507), who was the patron of Bernardo Tasso, fought in the imperial army of Charles V. Ferrante was a resolute defender of Neapolitan rights in the face of imposed Spanish institutions and when the Spanish Inquisition was introduced in Naples in 1552 he was obliged to flee to France.

The family owned 300 fiefs, 40 counties, nine marquisates, twelve duchies and ten principalities, primarily located in Calabria, Campania, Basilicata, and Apulia.