1521Centuries: 15th century - 16th century - 17th century
- January 3 - Pope Leo X excommunicates Martin Luther.
- January 28 - Diet of Worms begins, lasting until May 25.
- March 6 - Ferdinand Magellan discovers Guam
- March 16 - Ferdinand Magellan reaches the Philippines.
- April 27 - Battle of Mactan: Explorer Ferdinand Magellan is killed by natives in the Philippines.
- May - Outbreak of war between Emperor Charles and the King of France.
- May 20 - Battle of Pampeluna
- May 25 - The Diet of Worms ends when Charles V, Holy Roman Emperor issues the Edict of Worms, declaring Martin Luther an outlaw.
- June 30 - Battle of Esquiroz - French forces under Henri d'Albret, exiled King of Navarre, are defeated by the Spanish and forced to abandon their attempt to recover Henri's kingdom.
- August 29 - Capture of Belgrade by the Turkish army of Suleiman I after a brave resistance.
- November 23 - Spanish-German-Papal forces under Prosper Colonna force French Marshal Odet de Lautrec to abandon Milan.
- Cuautemoc, the last Aztec Emperor, surrenders to Spanish Conquistador Hernan Cortes