In general, the 16th century was the Age of Discovery. A major era in the history of the world. Its also the time of Henry VIII of England (and we all know what a drama that was).
April 1509: The Battle of Agnadello between the French (commanded by Louis XII) and Venetians (jointly commanded by Bartolomeo d'Alviano and Niccolò di Pitigliano) starts.
May 1509: The French are victorious in the Battle of Agnadello. Bartolomeo d'Alviano is captured as a Prisoner of War. Niccolò di Pitigliano retrieves The Shroud.
1510: Francesco Vecellio, an Assassin, assassinates Niccolò di Pitigliano and retrieves The Shroud.
May 1510: Caterina Sforza, an ally of the Assassins, dies.
1512: The Medici regain their power.
Mid-1512 : Rise of Martin Luther, founder of Protestantism movement.
1512: Copernicus completes Commentariolus, placing the sun at the center of the solar system.
1512: Florentine Republic dismantled; Medici regain power.
1512: Selim I forces his father Bayezid II to abdicate the throne of Ottoman Empire. Bayezid dies shortly afterwards.
1513: Niccolo Machiavelli completes his book, The Prince. (in AC:B, Machiavelli says he will write the book in honor of Ezio - I speculate this is when Ezio dies or sometime around this).
1513: Bartolomeo d'Alviano is freed from French prison.
Sep 1515: Selim I captures Tabriz without any resistance. Subjugates the Persian Shah.
Oct 1515: Bartolomeo d'Alviano, an Assassin and condottiero, is killed.
Feb 1516: Mary I of England is born.
Jun 1516: John III, King of Navarre and brother in law to Cesare Borgia, dies.
1516: Selim I invades the Holy Land (Syria & Egypt).
1516: Leonardo da Vinci accepts to work at the court of Francis I, King of France.
1517: the Holy Land falls to the Ottoman Empire under Selim I, declares himself Caliph.
1517: Martin Luther publishes is 95 Theses, sparking the Protestant Reformation in Europe.
1519: Leonardo da Vinci completes the Mona Lisa in France.
1519: Hernan Cortez lands in Central America, meets the Aztecs.
1519: Ferdinand Magellan leaves Europe to circle the globe.
1519: First civil riots occur in Anatolia (Ottoman Empire)
May 1519: Leonardo da Vinci dies.
June 1519: Lucrezia Borgia, daughter of Rodrigo Borgia, dies.
1520: The fleet of Hernán Cortés arrives in Mexico.
1520: Giovanni Borgia gets the Crystal Skull.
1520:Bombastus analyzes the Crystal Skull.
1520: Selim I dies (possibly poisoned). Succeeded by his son Suleiman I (the Magnificent), ushering new era of growth in Ottoman Empire. Aleksandra Lisowska (Roxelana) is given to him as a gift. Initially a concubine, she later became his Queen, becomes the most influential figure in Ottoman politics.
1520: Aztec Empire destroyed.
1521: Martin Luther excommunicated.
1521: Ferdinand Magellan dies.
1521: Ottoman Empire advances into eastern Europe, capturing Belgrade.
1521: First son born to Suleiman I.
1522: Bianca Riario, daughter of Caterina Sforza dies.
1522: Suleiman I conquers island of Rhodes (Knights Hospitallers, who flee to island of Malta).
Dec 1524: Vasco da Gama, a Portuguese explorer and a Templar, dies.
1525: France and Ottoman Empire ally against the Holy Roman Empire.
1526: Suleiman I defeats King Louis II of Hungary and Bohemia in battle, who dies while retreating.
1527: Medici lose Florence again to supporters of Giralomo Savanorola, unti 1530.
1527: Spanish & German troops sack Rome.
Jun 1527: Niccolo Machiavelli an Assassin, dies, entombed in Sante Croce, Florence.
1529: Treaty of Zaragosa divides world's waters between Spain and Portugal; East for Spain, west for Portugal.
1529: Suleiman I launches military campaign into Hungary. Lays siege to Vienna, Austria. But he is finally defeated, halting the spread of Islam into Europe.
1529: Archduke Ferdinand of Austria dies (how convenient)
1532: The Prince is published.
1532: Suleiman I launches unsuccessful campaign into Hungary.
1533: Ottaviano Riario, son of Caterina Sforza, dies.
1533: Peace treaty divides Hungary between Austria and Ottoman Empire.
1533: Suleiman I makes Roxelana Queen of the Ottoman Empire.
Jun 1541: Francisco Pizarro y González, 1st Marquess of los Atabillos, is assassinated by Assassins.
Sep 1541: Philippus Aureolus Theophrastus Bombastus von Hohenheim, a Swiss Renaissance physician, botanist, alchemist, astrologer, and a member of the Assassin Order, dies.
1542: Giovanni Borgia, an Assassin, experiences a vision of an unknown Chinese man through the Crystal Skull and decides to alert the other Assassins.
May 1543: Niccolò Copernico, a Polish Renaissance astronomer, mathematician and priest, dies.
1548: Giovanni Borgia, an Assassin and son of Lucrezia Borgia and Perotto Calderon, dies.
1553: Queen Mary I obtains an Apple of Eden and begins her rule over England.
Mar 1554: Ivan Ivanovich, heir to the Russian throne, is born.
1560: Francesco Vecellio, an Assassin, dies.
Nov 1581: Tsarevich Ivan Ivanovich is assassinated by Assassins.
other events at this time:
- start of African slave trade
- Islamic conquest of Christian Ethiopia