An ancient Roman "municipium", the town has been the most important trade and manufacturing centre of the area for centuries. After the fall of the Roman Empire, Casale became a free municipality and, in the 15th and early 16th centuries, served as the capital of the House of Palaiologos. Then in 1536 the town passed to the Gonzagas who fortified it with a large citadel. In the 17th century Casale was heavily involved in the War of the Mantuan Succession and sieged by French and Spanish troops. During the wars of Italian unification the town was a defensive bulwark against the Austrian Empire.