Initially the ancient village of San Lorenzo alle Grotte was placed nearby the Lake of Bolsena. Its territory was characterized by many caves, hence the name San Lorenzo alle Grotte (grotte infact means caves).
Initially inhabited by the Etruscans, under the Roman domination San Lorenzo became City Hall and Prefecture of the Romans.
Dating back to this period is the legend that during an invasion of the Vandals in the fifth century P.C. the people invoked divine protection. After a while, at the approach of the barbarians, a thick fog which prevented the invaders from accomplishing their work descended.
Thanks to the proximity of the Via Cassia, the center always had a great strategic importance, so much to fuel the ongoing struggles of the local nobility and the Church.
In the eleventh century San Lorenzo was given by the Countess Matilde di Canossa, to the Church. Later the Republic of Orvieto and the Church alternated their ruling over it.
In the first half of the sixteenth century, the city was sacked and burned by mercenaries, traveling to Rome.
In the eighteenth century onwards, due to rising lake level, the area where once stood San Lorenzo Vecchio became rather unhealthy. So an initiative of Pius VI at first, and then of the apostolic treasurer Pope Clement XIV, transferred the population in a healthier area.
The new city project was entrusted to Francesco Navone, who, inspired to Amalienborg Square in Copenhagen, developed the city octagonally. In the chosen area it was then brought water and in 1774 it was finally founded San Lorenzo Nuovo, the “New” San Lorenzo indeed.
During the Renaissance, in 1867, Mount Ladro near San Lorenzo Nuovo, became the scene of many battles between partisans and Pontifice troops.
In World War II, the city suffered several air raids with many casualties and widespread damage.