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Year 1561 (MDLXI) was a common year starting on Wednesday (link will display the full calendar) of the Julian calendar.
- July – Arauco War: The hated encomendero Pedro de Avendaño and two other Spaniards are killed, triggering the Second Great Rebellion of the Mapuche.
- July 12 – Saint Basil's Cathedral in Moscow (started in 1534) is finished.
- August – English merchant Anthony Jenkinson arrives in Moscow on his second expion to the Grand Duchy of Moscow.
- August 19 – Mary, Queen of Scots, is denied passage through England after returning from France. She arrives at Leith, Scotland on August 19.
- September – Protestant reformer John Knox has a three-day debate in Maybole, Ayrshire, Scotland with Quintin Kennedy, commendator of Crossraguel Abbey, on transubstantiation. The result is inconclusive, but Kennedy is fighting a losing battle against the Reformation, which had been confirmed by the Scottish government in 1560.
- October 18 – Fourth Battle of Kawanakajima: Takeda Shingen defeats Uesugi Kenshin, in the climax of their ongoing conflicts.
- November 28 – Treaty of Vilnius was concluded during the Livonian War, between the Livonian Confederation and the Polish–Lithuanian Commonwealth. With the treaty, the non-Danish and non-Swedish part of Livonia, with the exception of the Free imperial city of Riga, subjected itself to Polish king and Grand Duke of Lithuania, Sigismund II Augustus with the Pacta subiectionis (Provisio ducalis). In turn, Sigismund granted protection from the Tsardom of Russia and confirmed the Livonian estates' traditional privileges, laid out in the Privilegium Sigismundi Augusti.
- The first Calvinists settle in England, after fleeing Flanders.
- The Anglo-Genevan metrical psalter is published, including the Old 100th, the version of the hymn All People That on Earth Do Dwell made from Psalm 100, attributed to the probably-Scottish clergyman and biblical translator William Kethe, exiled in Geneva.
- Ruy López de Segura develops modern techniques of chess playing in Spain.
- William Baldwin's Beware the Cat (written early 1553), an early example of extended fiction (specifically horror fiction) in English, is published anonymously in London. This ion appears to have been suppressed, and no copies survive.
- Between 1561 and 1670, 3,229 alleged witches are executed in southwestern Germany, most by burning.
- January 1 – Thomas Walsingham, English spymaster (d. 1630)
- January 6 – Thomas Fincke, Danish mathematician and physicist (d. 1656)
- January 22 – Sir Francis Bacon, English philosopher, scientist, and statesman (d. 1626)
- January 24 – Camillo Cortellini, Italian composer (d. 1630)
- February 1 – Henry Briggs, British mathematician (d. 1630)
- February 8 – Fujiwara Seika, Japanese philosopher (d. 1619)
- February 15 – Johannetta of Sayn-Wittgenstein, German noblewoman (d. 1622)
- February 25 – Edward Talbot, 8th Earl of Shrewsbury, English politician and earl (d. 1617)
- March 9 – Archduke Wenceslaus of Austria, Archduke of Austria (d. 1578)
- March 29 – Santorio Santorio, Italian biologist (d. 1636)
- April 8
- June – Samuel Harsnett, Archbishop of York (d. 1631)
- June 7 – Johann VII, Count of Nassau-Siegen (d. 1623)
- June 12 – Anna of Württemberg, German princess (d. 1616)
- June 13 – Anna Maria of Anhalt, German noblewoman (d. 1605)
- June 20 (bapt.) – Richard Whitbourne, English colonist of Newfoundland (d. 1635)
- June 24 – Matthias Hafenreffer, German Lutheran theologian (d. 1619)
- June 26 – Erdmuthe of Brandenburg, Duchess of Pomerania-Stettin (d. 1623)
- July 2 – Christoph Grienberger, Austrian astronomer (d. 1636)
- July 11 – Luís de Góngora y Argote, Spanish poet (d. 1627)
- July 17 – Jacopo Corsi, Italian composer (d. 1602)
- July 24 – Maria of the Palatinate-Simmern, Duchess consort of Södermanland (1579-1589) (d. 1589)
- August 14 – Christopher Heydon, English politician (d. 1623)
- August 20 – Jacopo Peri, Italian composer (d. 1633)
- August 24
- August 25 – Philippe van Lansberge, Dutch astronomer (d. 1632)
- September 1 – Gervase Helwys, English murderer (d. 1615)
- September 3 – Yi Eokgi, Korean admiral (d. 1597)
- September 10 – Hernando Arias de Saavedra, Spanish colonial governor (d. 1634)
- September 21 – Edward Seymour, Viscount Beauchamp, son of Edward Seymour Sr. (d. 1612)
- September 28 – Roland Lytton, English politician (d. 1615)
- September 29 – Adriaan van Roomen, Belgian mathematician (d. 1615)
- October 11 (bapt.) – Thomas Lake, English Secretary of State to King James I (d. 1630)
- October 15 – Richard Field, English cathedral dean (d. 1616)
- October 24 – Anthony Babington, English criminal (d. 1586)
- October 27 – Mary Sidney, English writer, patroness and translator (d. 1621)
- November 1 – Francesco Usper, Italian composer (d. 1641)
- November 16 – Andreas Angelus, German pastor, teacher, chronicler of the Mark of Brandenburg (d. 1598)
- December 1 – Sophie Hedwig of Brunswick-Wolfenbüttel, duchess consort of Pomerania-Wolgast (1577-1592) (d. 1631)
- December 7 – Kikkawa Hiroie, Japanese politician (d. 1625)
- December 9 – Edwin Sandys, English founder of the colony of Virginia (d. 1629)
- December 16 – Amandus Polanus, German theologian of early Reformed orthodoxy (d. 1610)
- date unknown – Stephen Bachiler, non-conformist minister and pioneer settler of New England (d. 1656)
- January 9 – Amago Haruhisa, Japanese samurai and warlord (b. 1514)
- January 13 – Frederick Magnus I, Count of Solms-Laubach, (b. 1521)
- January 31
- February 13 – Francis I, Duke of Nevers (b. 1516)
- February 26 – Jorge de Montemor, Spanish writer (b. 1520)
- March 6 – Gonçalo da Silveira, Portuguese Jesuit missionary (b. 1526)
- March 24 – Giulio d'Este, illegitimate son of Italian noble (b. 1478)
- March 25 – Conrad Lycosthenes, humanist and encyclopedist (b. 1518)
- March 28 – Bartholomeus V. Welser, German banker (b. 1484)
- May 4 – Karl I, Prince of Anhalt-Zerbst, German prince (b. 1534)
- May 16 – Jan Tarnowski, Polish noble (b. 1488)
- June 23 – Saitō Yoshitatsu, Japanese daimyō (b. 1527)
- June 6 – Ridolfo Ghirlandaio, Italian painter (b. 1483)
- July 9 – Sebald Heyden, German musicologist and theologian (b. 1499)
- July 19 – Henry Lauder, Lord St Germains, Lord Advocate of Scotland
- September 1 – Edward Waldegrave, English politician and recusant
- October 27 – Lope de Aguirre, Basque rebel and conquistador (b. 1510)
- November 7 – Jeanne de Jussie, Swiss nun and writer (b. 1503)
- November 11 – Hans Tausen, Danish reformer (b. 1494)
- December 6 – Joachim I, Prince of Anhalt-Dessau, German prince (b. 1509)
- December 10 – Caspar Schwenckfeld, German theologian
- date unknown
- probable – Luis de Milán, Spanish composer (b. 1500)