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 fourth 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. Constantinople would continue to serve as the capital of the Byzantine Empire even after the Western half of the Roman Empire collapsed in the late fifth century. Naturally, the Ottoman Empire would also use Constantinople as the capital of its empire after their conquest effectively ended the Byzantine Empire, and thanks to its strategic location, it has been a trading center for years and remains one today under the Turkish name of Istanbul.

The end of the Byzantine Empire had a profound effect not only on the Middle East but Europe as well. Constantinople had played a crucial part in the Crusades, and the fall of the Byzantines meant that the Ottomans now shared a border with Europe. The Islamic empire was viewed as a threat by the predominantly Christian continent to their west, and it took little time for different European nations to start clashing with the powerful Turks. In fact, the Ottomans would clash with Russians, Austrians, Venetians, Polish, and more before collapsing as a result of World War I, when they were part of the Central powers.

The Ottoman conquest of Constantinople also played a decisive role in fostering the Renaissance in Western Europe. The Byzantine Empire's influence had helped ensure that it was the custodian of various ancient texts, most notably from the ancient Greeks, and when Constantinople fell, Byzantine refugees flocked west to seek refuge in Europe.