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January 5 - Felix Manz, co-founder of the Swiss Anabaptists, was drowned in the Limmat in Zürich by the Zürich Reformed state church.

May 6 - Spanish and German troops led by the Duke of Bourbon sack Rome (the infamous Sacco di Roma), forcing Pope Clement VII to make peace with Charles V.

May 16 - Florentines drive out the Medici for a second time and Florence re-establishes a republic.

August 3 - First known letter was sent from North America by John Rut while at St. John's, Newfoundland.

August 20 - 60 Anabaptists meet at the Martyrs' Synod.

Spanish conquest of Guatemala highlands completed; first Guatemala City founded (Ciudad Vieja).

Spanish Conquistador Francisco de Montejo invades Yucatán.

Battle of Tokay - Ferdinand of Austria defeats John Zapolya and takes over most of Hungary. John appeals to the Turks for help.

Protestant Reformation begins in Sweden.

Ahmed Gragn of Somalia defeats the Ethiopian army with his new firearms.

People of the university of Wittenberg flee bubonic plague to Jena.

Bishop Vesey's Grammar School in Sutton Coldfield, West Midlands, UK is founded by Bishop John Vesey.

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March 21 - Hermann Finck, German composer and music theorist (died 1558)

April 14 - Abraham Ortelius, Flemish cartographer and geographer (died 1598)

July 13 - John Dee, English mathematician, astronomer, and geographer (died 1608)

July 31 - Maximilian II, Holy Roman Emperor (died 1576)

October 21 - Louis I, Cardinal of Guise, French cardinal (d. 1578)

Giuseppe Arcimboldo, Italian artist (died 1593)

Charles of Guise, French cardinal (died 1574)

Lawrence Humphrey, English clergyman and educator (died 1590)

Luis Ponce de León, Spanish lyric poet (died 1591)

Sakuma Nobumori, Japanese retainer and samurai (died 1581)

Annibale Padovano, Italian composer and organist (died 1575)

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January 5 - Felix Manz, leader of the Swiss Anabaptist (executed) (born 1498)

January 21 - Juan de Grijalva, Spanish conquistador (born 1489)

June 21 - Niccolò Machiavelli, Italian writer and statesman (born 1469)

July 28 - Rodrigo de Bastidas, Spanish conquistador and explorer (born c1460)

November 28 - Jerome Emser, German theologian (born 1477)

Boabdil, last Moorish king of Granada (born c1460)

Charles III, Duke of Bourbon, Count of Montpensier and Dauphin of Auvergne (born 1490)

Francesco Colonna, Italian Dominican priest (born 1433)

Thomas Docwra, Grand Prior of the Knights Hospitaller (born 1458)

Cristoforo Solari, Italian sculptor and architect (born c1460)

Jan "Ciezki" Tarnowski, Polish nobleman (born c1479)