The Duchy of Montferrat was created out of what was left of the March of Montferrat after the last Palaeologus heir had died (1533) and the margraviate had been briefly controlled by Spain (until 1536). After that brief interlude, it passed to the Gonzaga Dukes of Mantua. In 1574, Maximilian II, Holy Roman Emperor, raised Montferrat to the status of a duchy.
At that time, Montferrat had an area of 2750 km², and consisted of two separate parts bordered by the Duchy of Savoy, the Duchy of Milan, and the Republic of Genoa. Its capital was Casale Monferrato.
With the War of the Mantuan Succession (1628–1631), a piece of the duchy passed to Savoy; the remainder passed to Savoy in 1708, as Leopold I, Holy Roman Emperor, gained possession of the principal Gonzaga territory, the Duchy of Mantua.