| 1500: | In the Burji Mamluks empire, Zahir Kanauh overthrown by Ashraf Gan Balat. |
| 1501: | Isamil I establishes the Safavid dynasty in Persia, and the Twelve-Imam Shi'ism becomes the state religion. |
| 1507: | The Portuguese under d'Albuquerque establish strongholds in the Persian Gulf. |
| 1508: | Turkomans of the White Sheep empire, End of the White Sheep dynasty and the annexation of their territories by the Safawids. |
| 1511: | D'Albuquerque conquers Malacca from the Muslims. |
| 1517: | The Ottoman Sultan Selim Yavuz ("the Grim") defeats the Mamluks and conquers Egypt. |
| 1520: | The reign of Sulayman the Magnificent begins. |
| 1526: | Louis of Hungary dies at the Battle of Mohacs. |
| 1526: | The Battle of Panipat in India, and the Moghul conquest; Babur makes his capital at Delhi and Agra. |
| 1528: | The Ottomans take Buda in Hungary. |
| 1529: | Unsuccessful Ottoman siege of Vienna. |
| 1550: | The architect Sinan builds the Suleymaniye mosque in Istanbul. |
| 1550: | The rise of the Muslim kingdom of Atjeh in Sumatra. |
| 1550: | Islam spreads to Java, the Moluccas, and Borneo. |
| 1556: | The death of Sulayman the Magnificent. |
| 1568: | Alpujarra uprising of the Moriscos (Muslims forcibly converted to Catholicism) in Spain. |
| 1571: | The Ottomans are defeated at the naval Battle of Lepanto, and their dominance in the Mediterranean is brought to a close. |
| 1578: | The Battle of the Three Kings at Qasr al-Kabir in Morocco. King Sebastian of Portugal is killed. |
| 1588: | Reign of Safavid Sultan Shah Abbas I begins. |
| 1591: | Mustaili Ismailis split into Sulaymanis and Daudis. |