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1621 ( MDCXXI) was a common year starting on Friday of the Gregorian calendar and a common year starting on Monday of the Julian calendar, the 1621st year of the Common Era (CE) and (AD) designations, the 621st year of the Anno Domini 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.
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 sets sail from Mayflower 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 – Battle of Neu Titschein: Remnants of the Bohemian army temporarily hold off the Imperial advance in Silesia.
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. September–October –
Battle of Khotyn: Polish troops hold off a large Ottoman army for over a month.  October – The
Pilgrims of Plymouth Colony and Wampanoags celebrate a harvest feast (three days), later regarded as the , noted for peaceful First Thanksgiving 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 arrives at Fortune Plymouth Colony, with 35 more settlers. December – The Dutch mathematician and astronomer,
Willebrord Snel van Royen (1580-1626), reveals he has rediscovered the law of refraction, also known as Snellius' law.  December 31 – Thirty Years' War: The Peace of Nikolsburg is signed between Ferdinand II, Holy Roman Emperor and Gabor Bethlen, Prince of Transylvania. Bethlen agrees to renounce his claims to Hungary. In return Bethlen receives several counties and lands along the eastern border of the Holy Roman Empire, and Moravia is granted religious freedom.
January 16 – Magnus Celsius, Swedish astronomer and mathematician (d. 1679)
January 27 – Thomas Willis, English doctor who played 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)
February 14 – 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) February –
Lamoral II Claudius Franz, Count of Thurn and Taxis, Postmaster General of the Holy Roman Empire (1646-1676) (d. 1676)
March 1 – John Alleyn, Cornish barrister (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 16 – Georg Neumark, German poet and composer of hymns (d. 1681)
March 24 – John VI, Prince of Anhalt-Zerbst (1621-1667) (d. 1667)
March 26 (bapt.) – Jacob van der Ulft, Dutch painter (d. 1689)
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)
July 1 – Cornelis de Man, Dutch painter (d. 1706)
July 24 – Jan Andrzej Morsztyn, Polish poet (d. 1693)
August 12 – Albert d'Orville, Jesuit priest and missionary, cartographer (d. 1662)
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, English Member of Parliament (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 8 – Maximilian Henry of Bavaria, Roman Catholic bishop (d. 1688)
October 18 – Michael Angelo Immenraet, Flemish painter (d. 1683)
October 20 – ?ehzade Ömer, Ottoman prince (d. 1622)
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)
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) December 23
January 15 – Christopher Pickering, British politician (b. 1556) 
January 28 – Pope Paul V (b. 1552)
January 29 – Francis Taylor, Mayor of Dublin, Ireland (b. c. 1550)
February 10 – Pietro Aldobrandini, Italian cardinal, patron of the arts (b. 1571)
February 15 – Michael Praetorius, German composer (b. 1571)
February 16 – Sir Thomas Gerard, 1st Baronet, English Member of Parliament (b. 1560)
February 28 – Cosimo II de' Medici, Grand Duke of Tuscany (b. 1590)
March 4 – Ana de Jesús, Spanish Discalced Carmelite nun, spiritual writer and Servant of God (b. 1545)
March 8 – Enevold Kruse, Danish noble (b. 1554)
March 27 – Benedetto Giustiniani, Italian Catholic cardinal (b. 1554)
March 28 – Ottavio Rinuccini, Italian composer (b. 1562) March 31 – King Philip III of Spain, (Philip II of Portugal) (b. 1578)
April 1 – Cristofano Allori, Italian painter (b. 1577)
April 18 – Bridget Chaworth, English noble (b. 1542)
April 21 – Anne of Ostfriesland, German noblewoman (b. 1562) April –
John Carver, first governor of Plymouth Colony
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 8 – Anne de Xainctonge, French Roman Catholic nun (b. 1567)
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 19 – Don Giovanni de' Medici, Italian military commander and diplomat (b. 1567)
July 30 – Rudolph, Prince of Anhalt-Zerbst (b. 1576)
August 7 – Count Jobst of Limburg (b. 1560)
August 13 – John Berchmans, Belgian Jesuit scholastic and saint (b. 1599)
August 15 – John Barclay, Scottish writer (b. 1582)
August 23 – Antonio il Verso, Italian composer (b. 1565)
August 30 – Bah al-d?n al-mil?, one of the main co-founders of Isfahan School of Islamic Philosophy (b. 1547)
September 7 – Peter Warburton, English Justice of the Common Plea (b. 1540)
September 17 – Robert Bellarmine, Italian Roman Catholic bishop, saint, proponent of futurism (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)
Philbrick, Nathaniel (2006). . New York: Penguin Books. p. 84. Mayflower: A Story of Community, Courage and War ISBN . 978-0-14-311197-9
^ Tucker, S.C., editor, 2010, A Global Chronology of Conflict, Vol. Two, Santa Barbara: ABC-CLIO, LLC,
George Sarton (1936). . Saint Catherine Press Limited. p. 724-725. A Volume of Studies on the History of Mathematics and the History of Science: Presented to Professor David Eugene Smith on His 76th Birthday (Jan. 21, 1936)
Maurice Willmore Barley; Council for British Archaeology (1977). . Published for the Council for British Archaeology by Academic Press. p. 117. European towns: their archaeology and early history ISBN . 978-0-12-078850-7
"PICKERING, Christopher (c.1556-1621), of Threlkeld, Cumb.; later of Ormside alias Prinshead, Westmld". History of Parliament . Retrieved 2018.