The mythical origins of the town have their roots in legend; it is told that it was Hercules who founded the town when he arrived at Sezze after conquering the Lestrigons.
The town probably had Latin origins in Volschi territory and then passed under the direct control of Rome. Sezze had numerous battles with the neighbouring towns, especially against Priverno and this was why it was fortified by the Romans. In 382 B.C. the town became a Latin colony.
At the time of the Social War the town took the side of Marius, but in 82 B.C. it fell into the hands of Silla and was besieged. During the imperial period Sezze enjoyed a certain prestige as a flourishing agricultural centre and was appreciated for the production of good wine.
It passed under the control of the Church and for a short period was part of the domain of the Counts of Tusculum, first of all, and then of the Frangipane later, under the control of the Holy Seat.
During the later Middle Ages the town managed to survive thanks to its fortified position and from 956 it organised itself as a free commune. Just after 1000 Lidano d’Antena, the future patron of the town had the monastery of Saint Cecilia built and ordered the surrounding area to be reclaimed.
Illustrious people and various popes stayed at Sezze for short periods, including Pope Gregory VII, Pasquale II and Lucio III.
At the end of the fourteenth century the Caetani family, which already held control of most of southern Lazio, took possession of Sezze for a further twelve years, after which the population rebelled and booted out the lords.
A serious plague epidemic struck the town in 1656 decimating the population and bands of Spanish and Austrian soldiers struck the town that already had no strength left.
In 1798 Napoleon’s troops attacked Sezze but were driven out by the local population.