The first Smyrniote crusade was the brainchild of Clement VI. The threat of Turkish piracy in the Aegean Sea had induced Clement's predecessors, John XXII and Benedict XII, to maintain a fleet of four galleys there to defend Christian shipping, but starting in the 1340s Clement endeavoured with Venetian aid to expand this effort into a full military expedition. He commissioned Henry of Asti, the Catholic patriarch of Constantinople, to organise a league against the Turks, who had increased their piracy in the Aegean in recent years. Hugh IV of Cyprus and the Order of the Hospital joined and, on 2 November 1342, the Pope sent letters to engage the men and ships of Venice. The Papal bull granting the Crusade indulgence and authorising its preaching throughout Europe, Insurgentibus contra fidem, was published on 30 September.
The first Smyrniote crusade began with a string of naval victories and ended with a successful assault on Smyrna, capturing the harbour and the citadel but not the acropolis, on 28 October 1344. In a gesture of over-confidence, on 17 January 1345 Henry of Asti attempted to celebrate mass in an abandoned structure which he believed had been the cathedral of the metropolitan. In the middle of the service Umur Beg swept down on the congregation. In the ensuing slaughter the leaders of the crusade were killed, including the Patriarch, Martino Zaccaria and the Venetian commander Pietro Zeno.
The precarious situation of the Crusaders in Asia spurred the Pope to organise a second expedition in 1345. In November, under the command of Humbert II of Viennois, the second Smyrniote crusade set out from Venice. In February 1346 it won a victory over the Turks at Mytilene, but Humbert did little more at Smyrna than sortie against the Turks and refortify the Christian section of the city. The next five years were occupied by Clement VI with attempts to negotiate a truce with the Turks, who kept Smyrna in a constant state of siege by land, and direct financial and military aid to the city. Although his concern with the Crusade ended abruptly in September 1351, the city of Smyrna remained in Christian hands until 1402.
- Kenneth Meyer Setton. 1976. The Papacy and the Levant, 1204–1571, vol. I. Philadelphia: American Philosophical Society, pp. 184–223.
- Jules Gay. 1904. Le pape Clément VI et les affaires d'Orient. PhD thesis.