Monte Romano, like so many of the towns in the Maremma Laziale, has Etruscan origins, as can be seen by the many tombs in the area, especially Norchia. However, the area was mainly of agricultural importance.

The actual town of Monte Romano was officially founded in 1456 when Pope Callisto III sold an old fortress, Rocca Respampani dominating the Traponzo torrent, to the Santo Spirito family. The family immediately decided to build a new town, originally intending to use the fortress for this purpose. However, this was a mere ruin and so in the 17-18th Century the town we see today was built around a small church and inn.