Orpierre was an essential stopover for travellers on the "Route des Princes d'Orange", which linked Avignon, City of the Popes, to Rome.
The town was a Calvinist stronghold and many Huguenots flocked here following Saint Barthelme. The Church, which was destroyed in 1560, would not be rebuilt before 1631 with the name of Saint Julian.
On the death of William III in 1702, Orpierre was allocated to the Prince of Conti and became definitively French.
Orpierre is amongst the most picturesque small towns in France. A heritage centre explores winemaking.