During the reign of Constantine I, the First Crusade took place. An army of Western European Christians marched through Anatolia and Cilicia on their way to Jerusalem. The Armenians in Cilicia gained powerful allies among the Frankish Crusaders, whose leader, Godfrey de Bouillon, was considered a savior for the Armenians. Constantine saw the Crusaders' arrival as a one-time opportunity to consolidate his rule of Cilicia by eliminating the remaining Byzantine strongholds in the region. With the Crusaders' help, they secured Cilicia from the Byzantines and Turks, both by direct military actions in Cilicia and by establishing Crusader states in Antioch, Edessa, and Tripoli. The Armenians also helped the Crusaders.

To show their appreciation to their Armenian allies, the Crusaders honored Constantine with the titles of Comes and Baron. The friendly relationship between the Armenians and Crusaders was cemented by frequent intermarriages. For instance, Joscelin I, Count of Edessa married the daughter of Constantine, and Baldwin, brother of Godfrey, married Constantine's niece, daughter of his brother T'oros. The Armenians and Crusaders were part allies, part rivals for the two centuries to come.