Campus Mellis rose probably over the roof Apiola, a very ancient Latin city, destroyed by Tarquinius Priscus, fifth king of Rome (579 BC); the ruins of Apiola are visible 6 kilometres (4 mi) away from the present-day historic center of Campodimele.
In the 6th century AD, the Lombards established the first fortified settlement, while in the following century it was part of the possessions of the Monastery of Montecassino.
From 916, it was acquired by the Duchy of Gaeta. Campo de Melle is mentioned again in a donation by the Consul of Fondi in 1072. In 1087, Pope Victor III had a list of the abbey's property sculpted onto the bronze door of the Basilica of Montecassino. In 1384, it became a possession of the Caetani family of Fondi, but, in 1497, King Frederick IV of Naples gave the county of Fondi with the surrounding duchies, including Campodimele, to the Colonna family.
In 1534, Giulia Gonzaga fled here from the Algerian pirate Hayreddin Barbarossa. In 1591, the fief was inherited by Luigi Carafa, Prince of Stigliano.
Campodimele gained municipal rights in 1813.
