Events of 1521

January–June

March–April:Ferdinand Magellan's voyage around the world

• 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 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 – 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.

• May – War breaks out between Charles V, Holy Roman Emperor and 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: Martin Luther outlaw.

• May 25 – The Diet of Worms ends when Charles V, Holy Roman Emperor issues the Edict of Worms, declaring Martin Luther an outlaw.

• 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.

July–December

• 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 I.

• November 23 – Spanish–German–Papal forces under Prosper Colonna force French Marshal Odet de Lautrec to abandon Milan.

Undated

• Berengairo da Garbi notices the appendix.

• San Juan Bautista is founded in the Puerto Rican archipelago.

• Ryazan is captured by Moscow.

• The first child is born by Roxelana to Suleyman the Magnificent.

Births

• 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

• *Anne Askew, English Protestant martyr (d. 1546)

• *John Aylmer, English divine (d. 1594)

• *Thomas Chaloner, English statesman and poet (d. 1565)

• *Philippe de Monte, Flemish composer (d. 1603)

• *Thomas Wyatt the younger, English rebel (d. 1554)

Deaths

• 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)

• December 1 – Pope Leo X (b. 1475)

• December 13 – King Manuel I of Portugal (b. 1469)

• date unknown

• *Edward Poyning, Lord Deputy to King Henry VII of England (b. 1459)

• *Stephen Hawes, English poet (b. 1502)