| 1542–1549 | New Spain, Central America [colonization] | The Spanish conquistador leader Francisco de Montejo subdues bitter resistance by the Maya in the southern half of the Yucatán Peninsula in Central America. Their resistance causes him to abandon attempts to conquer the rest of the peninsula. |
| 1545–1547 | Italy [Catholicism] | The first session of the Council of Trent is held in Trent, Italy. A council of the Roman Catholic Church, it is convened to formulate a response to the spread of Protestantism. Other sessions open in 1551 and 1562. |
| 1546 | England [statistics and demography] | The population of England is more than 4 million. |
| 1546 | Flanders [earth sciences] | Flemish cartographer Gerardus Mercator states that the Earth must have a magnetic pole separate from its ‘true’ pole, in order to explain the deviation of a compass needle from true North. |
| 1546 | Italy [medicine] | The Italian physician Girolamo Fracastoro publishes De contagione et contagiosis morbis et curatione/On Contagion and the Cure of Contagious Disease, in which he describes typhus for the first time, and also proposes that diseases are spread through microscopic bodies. |
| 18 February 1546 | Holy Roman Empire, Saxony [political events] | Martin Luther, great German theologian, preacher, biblical translator, and instigator of the Protestant Reformation, dies in Eisleben, Saxony (now Germany), while trying to negotiate between the landgraves of Mansfeld, as Germany rushes towards religious war (62). |
| 7 June 1546 | England, France [treaties] | The Peace of Ardres ends England's war with France and Scotland. The northern French port of Boulogne is to remain English for eight years and then be restored to France; King Francis I of France undertakes to pay King Henry VIII of England a 94,736-crown pension and 50,000 crowns to his successors. |
| July 1546 | Holy Roman Empire [Schmalkaldic War (1546–53)] | The army of the German Protestant Schmalkaldic League, under Sebastian Schärtlin von Burtenbach, occupies the free city of Donauwörth; its strategy in the Schmalkaldic War is to occupy the Habsburg Tirol, thus isolating Germany from reinforcement from Italy. |
| September - November 1546 | Holy Roman Empire, Germany [Schmalkaldic War (1546–53)] | The Holy Roman Emperor Charles V takes the cities of Memmingen, Biberach, Heilbronn, Esslingen, and Reutlingen; the Protestant Schmalkaldic League in Swabia disintegrates. |
| 14 December 1546 | Scandinavia [births and deaths] | Tycho Brahe, leading Danish astronomer, teacher of Johannes Kepler, born in Knudstrup, Scania, Denmark-Norway (–1601). |
| 23 December - 29 December 1546 | Holy Roman Empire [Schmalkaldic War (1546–53)] | The Schmalkaldic cities of Ulm and Frankfurt submit to the Holy Roman Emperor Charles V, bringing his forces to the border of the most powerful Protestant Schmalkaldic leader, Philip, Landgrave of Hesse. |
