Giovanni II Paleologo, the Marquis of Monferrato, started construction on the current castle, and it was completed by 1357.
Casale took on the role of capital within the Monferrato marquisate, obtaining city status in 1474, and the castle, the seat of the court, changed its appearance following the renovations of the marquises Guglielmo VIII (1464-1483) and Bonifacio V (1483-1494).
With the transfer of Casale to the Gonzagas of Mantua, following the death of the last Paleologo marquis, the castle was reinforced. In response to new military techniques, the walls were heavily reworked and the castle took on the hexagonal shape still seen today. The towers were reinforced and four new ravelins were built. At the start of the 17th century, the castle was once again the seat of a court. For diplomatic reasons, the dukes of Mantua, occupied with frequent negotiations with the Savoys, would stay here. The castle went through another period of splendour during the principality of Duke Carlo II Gonzaga-Nevers (1637-1665), who often stayed in the city with his court, giving a considerable boost to Casale's social and cultural life.
With the crisis in the Gonzaga dynasty, Casale's castle went into a steady decline. After the handover of the city and Monferrato to the Savoys in 1708, the castle began a long period of use as barracks.
In the middle of the 19th century Casale was fortified in anticipation of a war with Austria, and the castle was incorporated into the defensive system. The Savoy state decided to knock down the eastern ravelin, the one turned towards the city. This allowed the creation of a vast public space, the current Piazza Castello, which could be used as a marketplace. With Italian unification, the other three ravelins became superfluous, and were also demolished.