During the fourteenth century the Eastern Mediterranean underwent a dramatic political and religious transformation. The Mamluk sultanate of Egypt maintained control of the Holy Land and the southern Levantine regions, but in Asia Minor, Greece, and the Balkans the rising Anatolian Turkish principalities began to replace previous Byzantine, Frankish, and Serbo-Bulgarian domination. In this century, the planning and launching of a crusade to the East changed in accordance with this new reality, both in terms of who initiated a crusade and against whom one was aimed. Although a desire to liberate Jerusalem never died out, it is safe to say that the fourteenth century witnessed a change in crusade impetus, as proposals to defend Christian territories from Turkish advances came to dominate crusading strategy. In other theatres too, great changes were underfoot during this period. In Iberia the kingdoms of Castile, Aragon-Catalonia, and Portugal gradually pushed the Moors from all but the southernmost regions of the peninsula, and in north-eastern Europe the Catholic rulers launched increasingly successful campaigns to convert and subject the Lithuanians and other Baltic peoples, as well as to defend their territories from Tartar incursions.

The pontificate of Benedict XII was sandwiched between two of the most active crusading popes of the century, John XXII (1316–1334) and Clement VI (1342–1352). Their dedication to the crusade was characterized by a vigorous response to the Turkish threat, reflected by two of the most significant crusading enterprises of the period: the naval league launched in the Aegean in 1333–1334, and the crusade of Smyrna in 1343–1352.