The first ruler of the castle was the local Baron of Sax/Misox, who by the 13th century ruled over the entire Val Mesolcina and controlled a number of castles. By the end of the century, the baron's power crossed over the San Bernardino Pass and by the 14th century they reached the peak of their power. Baron Albert von Sax-Misox was a founding member of the Grey League and the family's future looked bright. However, Albert's murder in 1406 led to the gradual decline of the family. In 1480 they sold Mesocco castle and its associated demesne to General Giacomo Trivulzio.