|Covid-19|February 9 – Papal Conclave of 1621: Pope Gregory XV succeeds Pope Paul V as the 234th pope.
February 17 – Myles Standish is appointed as the first commander of Plymouth Colony.
March 16 – Samoset, a Mohegan, visits the settlers of Plymouth Colony and greets them, "Welcome, Englishmen! My name is Samoset."
March 22 – The Pilgrims of Plymouth Colony sign a peace treaty with Massasoit of the Wampanoags.
March 31 – King Philip IV of Spain begins his 44-year rule.
April – The Twelve Years' Truce between the Dutch Republic and the Spanish Empire expires, and both sides prepare to resume the Eighty Years' War.
April 1 – The Plymouth, Massachusetts colonists create the first treaty with native Americans.
April 5 – The Mayflower sets sail from Plymouth on a return trip to England.
May 2 – The Panama earthquake affects the Isthmus of Panama with an estimated magnitude of 6.9 and a maximum Mercalli intensity of VII (Very strong).
May 24 – The Protestant Union is formally dissolved.
June 3 – The Dutch West India Company is founded.
June 21 – Thirty Years' War: Twenty-seven Czech lords are executed on the Old Town Square in Prague as a consequence of the Battle of White Mountain.
June 24 – Huguenot rebellions: Saint-Jean-d'Angély is taken after a 26-day siege by Royal forces.
July 25 – Thirty Years' War: The Battle of Neu Titschein is fought; remnants of the Bohemian army manage to hold off the Imperial advance in Silesia for the moment.
September–October – Battle of Khotyn: Polish troops hold off a large Ottoman army for over a month.
August – Huguenot rebellions: Louis XIII of France besieges the Huguenot city of Montauban in the Siege of Montauban, but is forced to abandon his siege two months later.
October – The Pilgrims of Plymouth Colony and Wampanoags celebrate a harvest feast (3 days), later regarded as the "First Thanksgiving", noted for peaceful co-existence.
October 9 – The Treaty of Khotyn is signed between the Ottoman Empire and the Polish–Lithuanian Commonwealth, ending the First Polish-Ottoman War.
November 11 – The ship Fortune arrives at Plymouth Colony, with 35 more settlers.
December 31 – Thirty Years' War: The Peace of Nikolsburg is signed between Ferdinand II, Holy Roman Emperor and Gabor Bethlen, Prince of Transylvania. Bethlen agreed to renounce his claims to Hungary. In return Bethlen received several counties and lands along the eastern border of the Holy Roman Empire, and Moravia was granted religious freedom.
The Venezuelan city of Petare is founded by Spanish conquistadors as San Jose de Guanarito.
The Swedish city of Gothenburg is founded by King Gustavus Adolphus of Sweden. The king also grants city rights to Luleå, Piteå and Torneå (Tornio). Riga falls under the rule of Sweden.
The Dutch mathematician and astronomer, Willebrord Snel van Royen (1580–1626), discovers the famous law of refraction, also known as "Snellius' law".
Tamblot starts the Tamblot Uprising
The Dutch East India Company sends 2000 soldiers under the command of Jan Pieterszoon Coen to the Banda Islands in order to force the local inhabitants to accept the Dutch trade monopoly on the lucrative nutmeg, grown almost exclusively on the Banda islands. The soldiers proceed to massacre most of the 15,000 indigenous inhabitants.
January 3 – Claude Maltret, French Jesuit (d. 1674)
January 16 – Magnus Celsius, Swedish astronomer and mathematician (d. 1679)
January 27 – Thomas Willis, English doctor who plays an important part in the history of anatomy (d. 1675)
January 30 – George II Rákóczi, Hungarian nobleman (d. 1660)
February 2 – Johannes Schefferus, Alsatian-born humanist (d. 1679)
February 4 – Frederick, Burgrave of Dohna, Dutch officer, and governor of Orange (d. 1688)
Lamoral II Claudius Franz, Count of Thurn and Taxis, German nobleman and Postmaster General of the Holy Roman Empire (1646–1676) (d. 1676)
Sibylla Schwarz, German poet (d. 1638)
February 20 – Erzsébet Thurzó, Hungarian noblewoman (d. 1642)
February 21 – Rebecca Nurse, Massachusetts colonist, executed as a witch (d. 1692)
March 1 – John Alleyn, Cornish politician (d. 1663)
March 2 – Louis Günther II, Count of Schwarzburg-Ebeleben (1642–1681) (d. 1681)
March 9 – Egbert van der Poel, Dutch painter (d. 1664)
March 15 – Georg Neumark, German poet and composer of hymns (d. 1681)
March 24 – John VI, Prince of Anhalt-Zerbst (1621–1667) (d. 1667)
March 27 – Margrave Charles Magnus of Baden-Durlach (d. 1658)
March 28 – Heinrich Schwemmer, German music teacher and composer (d. 1696)
March 31 – Andrew Marvell, English metaphysical poet and politician (d. 1678)
April 1 – Guru Tegh Bahadur, 9th Sikh Guru (d. 1675)
April 7 – Crato, Count of Nassau-Saarbrücken (1640–1642) (d. 1642)
Henry Vaughan, Welsh author (d. 1695)
Thomas Vaughan, Welsh philosopher (d. 1666)
Georg Arnold, Austrian musician (d. 1676)
William Penn, English admiral and politician (d. 1670)
April 25 – Roger Boyle, 1st Earl of Orrery, Anglo-Irish soldier, statesman and dramatist (d. 1679)
May 25 – David Beck, Dutch portrait painter (d. 1656)
June 1 – Jacob van der Ulft, Dutch painter (d. 1689)
Rutger von Ascheberg, Courland-born soldier in Swedish service (d. 1693)
Jørgen Bjelke, Norwegian officer and nobleman (d. 1696)
Isaac van Ostade, Dutch painter (d. 1649)
June 6 – Petar Zrinski, Croatian viceroy (executed 1671)
June 16 – Edward Proger, Member of Parliament for Brecknockshire (d. 1713)
June 29 – Willem van der Zaan, Dutch Admiral (d. 1669)
July 1 – Cornelis de Man, Dutch painter (d. 1706)
Jean de La Fontaine, French writer (d. 1695)
Leonora Christina Ulfeldt, Danish countess (d. 1698)
Anthony Ashley Cooper, 1st Earl of Shaftesbury, English politician (d. 1683)
Thomas Hanford, New England settler and puritan minister (d. 1693)
Kinoshita Jun'an, Japanese philosopher and Confucian scholar (d. 1699)
July 24 – Jan Andrzej Morsztyn, Polish poet (d. 1693)
August 12 – Albert d'Orville, Jesuit priest and missionary, cartographer (d. 1662)
Sir John Pakington, 2nd Baronet, English politician (d. 1680)
Israel Silvestre, French topographical etcher (d. 1691)
August 19 – Gerbrand van den Eeckhout, Dutch painter (d. 1674)
August 22 – Adriaen van Gaesbeeck, Dutch painter of genre subjects and portraits (d. 1650)
August 28 – Sir Richard Grobham Howe, 2nd Baronet, Member of Parliament of England (d. 1703)
September 8 – Louis, Grand Condé, French general (d. 1686)
September 9 – Henry X, Count of Reuss-Lobenstein, Rector of the University of Leipzig (d. 1671)
October 3 – Friedrich Werner, German musician (d. 1660)
October 8 – Maximilian Henry of Bavaria, Roman Catholic bishop (d. 1688)
October 18 – Michael Angelo Immenraet, Flemish painter (d. 1683)
October 20 – Şehzade Ömer, Ottoman prince (d. 1622)
Nicholas Barré, French Minim friar, priest and founder (d. 1686)
Richard Standish, English politician (d. 1662)
October 23 – Lord John Stewart, Scottish aristocrat, Royalist commander in the English Civil War (d. 1644)
October 24 – Serafina of God, founder of seven Carmelite monasteries of nuns in southern Italy (d. 1699)
November 11 – Israel Tonge, English churchman and anti-Catholic conspirator (d. 1680)
Cornelis Geelvinck, Dutch mayor (d. 1689)
Henry Mordaunt, 2nd Earl of Peterborough, English diplomat (d. 1697)
December 3 – Bohuslav Balbín, Czech writer and Jesuit (d. 1688)
December 10 – Christian Albert, Burgrave and Count of Dohna, German nobleman and general in the army of Brandenburg (d. 1677)
December 12 – Gerard Pietersz Hulft, Dutch general (d. 1656)
Heneage Finch, 1st Earl of Nottingham, English politician (d. 1682)
Edmund Berry Godfrey, English magistrate whose mysterious death caused anti-Catholic uproar in England (d. 1678)
Approximate date – Richard Allestree, English churchman and provost of Eton College (d. 1681)
Françoise-Marie Jacquelin, Acadian heroine (d. 1645)
January 15 – Christopher Pickering, British politician (b. 1556)
January 28 – Pope Paul V (b. 1552)
January 29 – Francis Taylor, Mayor of Dublin (b. c. 1550)
February 10 – Pietro Aldobrandini, Italian Cardinal and patron of the arts (b. 1571)
February 15 – Michael Praetorius, German composer (b. 1571)
February 16 – Sir Thomas Gerard, 1st Baronet, Member of the Parliament of England (b. 1560)
February 28 – Cosimo II de' Medici, Grand Duke of Tuscany (b. 1590)
March 4 – Ana de Jesús, Spanish Discalced Carmelite nun and spiritual writer (b. 1545)
March 8 – Enevold Kruse, Danish noble (b. 1554)
March 27 – Benedetto Giustiniani, Catholic cardinal (b. 1554)
March 31 – King Philip III of Spain, (Philip II of Portugal) (b. 1578)
April 1 – Cristofano Allori, Italian painter (b. 1577)
Archduchess Maria Christina of Austria (b. 1574)
Edward Seymour, 1st Earl of Hertford (b. 1539)
April 15 – John Carver, first governor of Plymouth Colony
April 18 – Bridget Chaworth, English noble (b. 1542)
April 21 – Anne of Ostfriesland, German noblewoman (b. 1562)
May 3 – Elizabeth Bacon, English Tudor gentlewoman (b. 1541)
May 11 – Johann Arndt, German theologian (b. 1555)
May 15 – Hendrick de Keyser, Dutch architect and sculptor (b. 1565)
June 2 – Dorothea of Lorraine (b. 1545)
June 8 – Anne de Xainctonge, French saint (b. 1567)
Kryštof Harant z Polžic a Bezdružic, Bohemian composer, soldier, and author (executed) (b. 1564)
Maxmilián Hošťálek, Czech noble and politician (b. 1564)
Joachim Andreas von Schlick, Czech leader (b. 1569)
June 23 – Zsigmond Forgách, Hungarian noble and soldier (b. 1559)
June 26 – Christence Kruckow, Danish noble (b. 1558)
July 2 – Thomas Harriot, English astronomer and mathematician (b. c. 1560)
July 4 – Jean de Bonsi, Catholic cardinal (b. 1554)
July 10 – Charles Bonaventure de Longueval, Count of Bucquoy, soldier in Habsburg service (b. 1571)
July 13 – Albert VII, Archduke of Austria for a few months in 1619 and (b. 1559)
July 30 – Rudolph, Prince of Anhalt-Zerbst (b. 1576)
August 3 – Guillaume du Vair, French author and lawyer (b. 1556)
August 15 – John Barclay, Scottish writer (b. 1582)
August 23 – Antonio il Verso, Italian composer (b. 1565)
August 30 – Bahāʾ al-dīn al-ʿĀmilī, one of the main co-founders of Isfahan School of Islamic Philosophy (b. 1547)
September 7 – Peter Warburton, Justice of the Common Plea (b. 1540)
September 17 – Robert Bellarmine, Italian saint (b. 1542)
September 20 – Henry of Lorraine, Duke of Mayenne, French noble (b. 1578)
September 24 – Jan Karol Chodkiewicz, Polish military commander (b. 1560)
September 25 – Mary Sidney, English writer, patroness and translator (b. 1561)
October 8 – Antoine de Montchrestien, French dramatist and economist (b. c. 1575)
October 11 – Andrzej Sapieha, Polish nobleman (b. 1539)
October 16 – Jan Pieterszoon Sweelinck, Dutch composer (b. 1562)
October 19 – Imre Thurzó, Hungarian noble (b. 1598)
October 21 – Paul Phélypeaux de Pontchartrain, French politician (b. 1569)
November 26 – Ralph Agas, English surveyor (b. c. 1540)
December 4 – Andrew Willet, English theologian (b. 1562)
December 13 – Katarina Stenbock, queen of Gustav I of Sweden (b. 1535)
December 15 – Charles d'Albert, duc de Luynes, Constable of France (b. 1578)
1621 (MDCXXI) was a common year starting on Friday (dominical letter C) of the Gregorian calendar and a common year starting on Monday (dominical letter G) of the Julian calendar, the 1621st year of the Common Era (CE) and Anno Domini (AD) designations, the 621st year of the 2nd millennium, the 21st year of the 17th century, and the 2nd year of the 1620s decade. As of the start of 1621, the Gregorian calendar was 10 days ahead of the Julian calendar, which remained in localized use until 1923.