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|Centuries:||15th century – 16th century – 17th century|
|Decades:||1490s 1500s 1510s – 1520s – 1530s 1540s 1550s|
|Years:||1518 1519 1520 – 1521 – 1522 1523 1524|
|1521 by topic|
|Arts and science|
|Lists of leaders|
|Birth and death categories|
|Establishments and disestablishments categories|
|Ab urbe condita||2274|
|English Regnal year||12 Hen. 8 – 13 Hen. 8|
— to —辛巳年十二月初三日
|- Vikram Samvat||1577–1578|
|- Shaka Samvat||1443–1444|
|- Kali Yuga||4622–4623|
|- Ǹrí Ìgbò||521–522|
|Japanese calendar||Eishō 18Daiei 1
|Juche calendar||N/A (before 1912)|
|Julian calendar||1521 MDXXI|
|Minguo calendar||391 before ROC
|Thai solar calendar||2064|
|Wikimedia Commons has media related to: 1521|
- January 3 – Pope Leo X excommunicates Martin Luther in the papal bull Decet Romanum Pontificem.
- January 22 – Emperor Charles V opens the Diet of Worms.
- January 27 – Suleiman the Magnificent suppresses a revolt by the ruler of Damascus.
- January 28 – The Diet of Worms begins, lasting until May 25.
- March 6 – Ferdinand Magellan discovers Guam.
- March 16 – Ferdinand Magellan reaches the Philippines.
- April 7 – Ferdinand Magellan arrives at Cebu.
- April 16–April 18 – Martin Luther is examined before Emperor Charles V and the German Diet of Worms.
- April 24 – Revolt of the Comuneros – Battle of Villalar: Castilian royalists defeat the rebels and execute their three leaders.
- April 26 – Martin Luther leaves Worms and disappears for a year – he is rumored to be murdered, but is actually in hiding at the Wartburg Castle.
- April 27 – Magellan is killed in the Philippines, in the Battle of Mactan.
- May – War breaks out between Charles V, Holy Roman Emperor and Francis I, the King of France.
- May 17 – Edward Stafford, 3rd Duke of Buckingham, is executed for treason.
- May 20 – Battle of Pampeluna: The French defeat the Spanish.
- May 25 – The Diet of Worms ends when Charles V, Holy Roman Emperor issues the Edict of Worms, declaring Martin Luther an outlaw.
- May 27 – Jiajing Emperor ascends the throne of the Ming Dynasty.
- June 29 or June 30 – The first document is fully written in Romanian: the letter of Neacşu, a trader from Câmpulung, to Johannes Benkner, the mayor of Braşov, warning that the Ottoman Empire is preparing its troops to cross into Wallachia and Transylvania; the script used is Romanian Cyrillic.
- 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 8 – Battle of Tenochtitlan: Hernán Cortés and allied local Indians defeat the Aztec forces of Cuauhtémoc, the last Aztec Emperor.
- August 13 – Emperor Cuauhtémoc surrenders to Hernán Cortés.
- August 23 – Christian II of Denmark is deposed as king of Sweden and Gustav Vasa is elected regent.
- August 29 – Belgrade is captured by the Ottoman army of Suleiman the Magnificent.
- November 23 – Spanish–German–Papal forces under Prosper Colonna force French Marshal Odet de Lautrec to abandon Milan.
Date unknown 
- Jacopo Berengario da Carpi publishes Commentaria cum amplissimus additionibus super anatomiam Mundini in Bologna, including observation of the vermiform appendix.
- San Juan Bautista is founded in the Puerto Rican archipelago.
- Ryazan is annexed by Moscow.
- Student rebellion in Erfurt.
- March 21 – Maurice, Elector of Saxony (d. 1553)
- May 8 – Petrus Canisius, Dutch Jesuit (d. 1597)
- August 4 – Pope Urban VII (d. 1590)
- October 9 – Ottavio Farnese, Duke of Parma (d. 1586)
- December 1 – Takeda Shingen, Japanese warlord (d. 1573)
- December 13 – Pope Sixtus V (d. 1590)
- date unknown
- April 20 – Zhengde Emperor of China (b. 1491)
- April 25 – Juan López de Padilla, Juan Bravo and Francisco Maldonado, executed Spanish rebels
- April 27 – Ferdinand Magellan, Portuguese explorer (b. c. 1480)
- May 10 – Sebastian Brant, German humanist and satirist (b. 1457)
- May 17 – Edward Stafford, 3rd Duke of Buckingham (executed) (b. 1478)
- June 15 – Tamás Bakócz, Hungarian Catholic cardinal and statesman (b. 1442)
- June 21 – Leonardo Loredan, Doge of Venice (b. 1436)
- July – Juan Ponce de León, Spanish conquistador (b. 1460)
- August 27 – Josquin Des Prez, Flemish composer (b. c. 1450)
- October – Edward Poyning, Lord Deputy to King Henry VII of England (b. 1459)
- December 1 – Pope Leo X (b. 1475)
- December 13 – King Manuel I of Portugal (b. 1469)