|Covid-19|January – Battle of Naungyo, Burma, part of the Toungoo–Hanthawaddy War.
January 12 – Charles V, Holy Roman Emperor (and Charles I of Spain) and Francis I of France sign the Treaty of Toledo, agreeing to make no further alliances with England. The treaty comes after Henry VIII of England's split with Rome and Pope Paul III.
February 9 – First horse race held at Chester Racecourse, the oldest in use in England.
March – Canterbury Cathedral surrenders, and reverts to its previous status of 'a college of secular canons'.
May 30 – In Florida, Hernando de Soto lands at Tampa Bay with 600 soldiers with the goal to find gold. He also introduces pigs into North America.
May – The Six Articles, an Act of the Parliament of England, reaffirms certain Catholic principles in Henry VIII's Church of England.
August 15 King Francis I of France issues the Ordinance of Villers-Cotterêt that places the whole of France under the jurisdiction of the royal law courts and makes French the language of those courts and the official language of legal discourse.
September 7 – Guru Angad Dev becomes the second Guru of the Sikhs.
October 4 – Henry VIII contracts to marry Anne of Cleves.
November 1 Joachim II Hector introduces lutheranism in the Margraviate of Brandenburg, becoming the second Prince-Elector after the Prince-Elector of Saxony to turn Protestant.
Lutheranism is forcibly introduced into Iceland, despite the opposition of Bishop Jón Arason.
Beaulieu Abbey, Bolton Abbey, Colchester Abbey, Newstead Abbey, St Albans Abbey, St Mary's Abbey, York and Hartland Abbey (the last) fall prey to the Dissolution of the Monasteries in England.
First edition of the Calvinist Genevan psalter is published.
In Henan province, China, a severe drought with swarms of locusts is made worse by a major epidemic outbreak of the plague.
The first printing press in North America is set up in Mexico City.
Teseo Ambrogio's Introductio in Chaldaicam lingua, Syriaca atq Armenica, & dece alias linguas, published in Pavia, introduces several middle eastern languages to western Europe for the first time.
January 15 – Maeda Toshiie, Daimyo (d. 1599)
January 28 – Nicolò Donato, Doge of Venice (d. 1618)
February 13 – Elisabeth of Hesse, Electress Palatine by marriage (1576-1582) (d. 1582)
February 23 – Henry XI of Legnica, thrice Duke of Legnica (d. 1588)
February 23 – Salima Sultan Begum, Empress of the Mughal Empire as a wife of Emperor Akbar (d. 1612)
February 27 – Franciscus Raphelengius, Dutch printer (d. 1597)
March 5 – Christoph Pezel, German theologian (d. 1604)
March 18 – Maria of Nassau, Countess of Nassau (d. 1599)
April 5 – George Frederick, Margrave of Brandenburg-Ansbach (d. 1603)
April 6 – Amalia of Neuenahr, German noble (d. 1602)
April 7 – Tobias Stimmer, Swiss artist (d. 1584)
April 7 – Strange Jørgenssøn, Norwegian businessman (d. 1610)
April 30 – Archduchess Barbara of Austria, Austrian archduchess (d. 1572)
May 22 – Edward Seymour, 1st Earl of Hertford (d. 1621)
June 6 – Catherine Vasa, Regent of East Frisia (1599-1610) (d. 1610)
June 13 – Jost Amman, Swiss printmaker (d. 1591)
June 23 – William Darrell of Littlecote, politician (d. 1589)
July 4 – Louis VI, Elector Palatine (d. 1583)
September 18 – Louis Gonzaga, Duke of Nevers, Italian-French dignitary and diplomat (d. 1595)
October 1 – Peter Vok, Czech noble (d. 1611)
October 2 – Saint Charles Borromeo, Italian cardinal (d. 1584)
November 1 – Pierre Pithou, French lawyer and scholar (d. 1596)
December 5 – Fausto Paolo Sozzini, Italian theologian (d. 1604)
December 20 – Paulus Melissus, German composer (d. 1602)
December 31 – John Radcliffe, English politician (d. 1568)
José Luis Carvajal y de la Cueva, Portuguese explorer (d. 1590)
Hasegawa Tōhaku, Japanese painter (d. 1610)
Ikeda Katsumasa, Japanese military commander (d. 1578)
Laurence Tomson, Calvinist (d. 1608)
Humphrey Gilbert, English adventurer, explorer, member of parliament and soldier (d. 1583)
February 6 – John III, Duke of Cleves (b. 1491)
February 13 – Isabella d'Este, Marquise of Mantua (b. 1474)
March 5 – Nuno da Cunha, Portuguese governor in India (b. 1487)
March 12 – Thomas Boleyn, 1st Earl of Wiltshire, English diplomat and politician (b.1477)
April 17 – George, Duke of Saxony (b. 1471)
Guru Nanak, founder of Sikhism (b. 1469)
Ottaviano Petrucci, Italian printer (b. 1466)
July 5 – St Anthony Maria Zaccaria, Italian saint (b. 1502)
August – Vannoccio Biringuccio, Italian metallurgist (b. 1480)
September 8 – John Stokesley, English prelate (b. 1475)
November 15 – Hugh Cook Faringdon, Abbot of Reading
December 20 – Johannes Lupi, Flemish composer (b. c. 1506)
date unknown – James Beaton, Scottish church leader (b. 1473)
Year 1539 (MDXXXIX) was a common year starting on Wednesday (link will display the full calendar) of the Julian calendar.