In terms of geopolitics, perhaps the most seminal event of the Middle Ages was the successful Ottoman siege of Constantinople in 1453. The city had been an imperial capital as far back as the 4th century, when Constantine the Great shifted the power center of the Roman Empire there, effectively establishing two almost equally powerful halves of antiquity's greatest empire. The fall of Constantinople is still well-known today, but the Ottoman Empire was already pushing into Europe beforehand, and it would take repeated efforts by various European coalitions to prevent a complete Ottoman takeover of the continent. At the time, the most powerful European countries in Eastern Europe and the Balkans were Poland and Hungary. Russia was still throwing off the Mongol yoke, France and England were fighting an interminable war, Germany was broken into hundreds of entities, and the Holy Roman Empire was fighting the rise of Protestantism. The Italian merchant city-states of Venice and Genoa were intimately tied to the Balkans, the Byzantine Empire, the Black Sea, and the Ottomans. Genoa had been something of an Ottoman ally since the 1300s, even while the Ottomans were looming as a grave threat to Europe.

The Ottoman Sultan Murad II became known as the Ghazi Sultan and was seen as not only defending Islam against the Christians but also as a defender of other, less powerful Muslim beys. Thus, he gained support from Muslims both far and near before he turned his armies towards Venice, the Karamids, Serbia, and finally Hungary, which would get the Europeans' attention. In the historic tradition that already dated back over 300 years, a crusade was called to stop the Ottomans, and the main battle would be fought near Varna, a fortified city on the Black Sea coast of what is now Bulgaria. The result would set into motion the Ottomans' far more famous forays into Europe.