In Asia, the successors of the old Mongol Empire were in a state of gradual decline. The Ilkhanate had already fragmented into several political territories and factions struggling to place their puppet leaders over the shell of an old state; the Chagatai Khanate was undermined by religious unrest and fell to rebellion. The Black Plague swept through the Kipchak Khanate in 1346, and also affected the Genoese colonies under Mongol siege, thence spreading into Europe. The Yuan dynasty in China was struck by a series of disasters, including frequent flooding, widespread banditry, urban fire, declining grain, increased civil unrest and local rebellion – the seeds of resistance that would lead to its downfall. Southeast Asia remained free from Mongol power, with several small kingdoms struggling for survival.
In Europe, the decade continued the period of gradual economic decline, often mistitled the "depression" of the 1340s. This followed the end of the Medieval Warm Period and the start of the Little Ice Age in the 1300s, and affected most of Western Europe, with the exception of a few Italian city-states. The state increasingly interfered in the social and economic life of the decade, while Europe entered a period which saw almost continuous war for the next century. The Hundred Years' War (1337–1453) between France and England continued, and Edward III of England led an invasion resulting in notable victories at the Battles of Sluys and Crécy in 1340 and 1346 respectively. The medieval crusading spirit continued in Spain, with a Castilian victory at the Battle of Río Salado and the recommencement of the Reconquista in 1340; and in the Baltic, with King Magnus II of Sweden's Northern Crusades against Novgorod in 1347–1348. In the east, the Byzantine Empire, then under the Palaiologoi, saw the start of the disastrous Byzantine civil war of 1341–47. Meanwhile, a crisis of confidence in the Florentine banks caused many of them to collapse between 1341 and 1346. The Black Plague which struck Europe in 1348 wiped out a full third of the population by the end of the decade.
In Africa, the two great empires were the Christian Ethiopian Empire in the east and the Muslim Mali Empire in the west. Amda Seyon I, who had brought Ethiopia to its height, was succeeded in 1344 by Newaya Krestos, who continued to foster trade in East Africa. MansaSuleyman assumed office in the Mali Empire in 1341, and similarly took steep measures to reform Mali's finances. Songhai, which had emerged in this decade, was conquered by Mali for the time being.
The great flood in the river Periyar in modern-day southern India leads to the river changing its course, the closing of Muziris, the opening up of Cochin (Kochi) harbour, submersion of some islands, and birth of some new islands.
January 27 – Pope Clement VI issues his bill Unigenitus, defining the doctrine of "The Treasury of Merits" or "The Treasury of the Church" as the basis for the issuance of indulgences by the Catholic Church.
King Edward III of England introduces three new gold coins, the florin, leopard, and helm. Unfortunately, the amount of gold in the coins does not match their value of 6 shillings, 3 shillings, and 1 shilling and sixpence, so they have to be withdrawn and mostly melted down, by August of this year.
March 24 – Guy de Chauliac observes the planets Saturn, Jupiter, and Mars conjoined in the sky, under the sign of Aquarius, and a solar eclipse on the same day. This sign is interpreted as foreboding by many, and Chauliac will later blame it for the Black Plague.