Since the year 1000, Pisa had already consolidated its military and commercial dominion on the port of call of the modern Castiglione della Pescaia, called "Piscaria a mare" at the time, and, as a consequence, it ended by exercise its authority also on the castle and on its territories. Nevertheless, the Lombards family formally governed the area with the Church's approval.

Around the XIII century, the newly-born free town of Castiglione definitively headed towards the epoch of the Tuscan Republics, once it got rid of the feudal seigniory of the Lombardi of Buriano. In less than a century, Siena and Pisa's continuous political interference obliged the inhabitants of Castiglione to cede their rights and territories to these two cities, until the town was absorbed inside the two republics' borders.
In the XIV century, Siena already had the port, the fishing ground and the salt pits. In 1404, the inhabitants of Castiglione decided to submit to Florence, that was uninterruptedly ascending as fast as the other two republics were decaying.
The inhabitants of the small town repaired the ancient Pisan walls at their own expense, while the Medicean seigniory, once it completed the subjugation of Pisa (1509) and Siena (1559), engaged in reclamation works aiming at re-evaluating the insalubrious and marshy hinterland. The Medicis transferred here many Northern-born families and gave them the new sugar cane plantations, since they were considered the ideal cultivation in these humid areas. Moreover, they were supposed to facilitate the drainage of marshes, but this did not happen.
Instead, the Hapsburg-Lorraine family, who came to power in the Tuscan Grand Duchy in 1737 after the extinction of the Medici, carried out the most important reclamation works. This happened above all thanks to the Jesuit father Ximenes, who persuaded the Grand Duke Pietro Leopoldo of the necessity to operate in the territory so as to improve the inhabitants' miserable conditions. Therefore, great drainage works of marshes were performed and they were continued by Leopoldo II in 1824 and by the Grand Duke Ferdinando III, called "Canapone", in 1828.
This work also lasted after Castiglione was annexed to the Kingdom of Italy in 1859. In 1878, the Civil Engineering was born. It inherited the duties of the ancient Grand Duchy and provided for most of the reclamation in the plain. If the Genio Civile had the merit to accomplish most of the work, it was thanks to the Lorraine and their engagement on the reorganization of infrastructures and lands that this project could be started and adequately finished. Today, the town has about 7000 inhabitants.