The Black Death
Plague bacteria spread along Mongol trade routes from Central Asia to the Black Sea. In 1347 Genoese ships brought it to Sicily.
In five years it killed perhaps a third of Europe and the Middle East. Whole villages were abandoned, and people turned on Jews as scapegoats.
Survivors found labour scarce and wages higher. Serfdom weakened in the West, and the old order began to change.