|Covid-19|February 24 – Treaty of Nagyvárad: Peace is declared between Ferdinand I, Holy Roman Emperor and the Ottoman Empire. John Zápolya is recognized as King of Hungary (Eastern Hungarian Kingdom), while Ferdinand retains the northern and western parts of the Kingdom, and is recognized as heir to the throne.
April 26 – Battle of Las Salinas: Almagro is defeated by Francisco Pizarro, who then seizes Cusco.
June 18 – Truce of Nice: Peace is declared between Emperor Charles V and Francis I of France.
August 6 – Bogotá, Colombia is founded by Gonzalo Jiménez de Quesada.
September 28 – Battle of Preveza: The Ottoman fleet of Suleiman the Magnificent under the command of Hayreddin Barbarossa defeats the Holy League of Emperor Charles V under the command of Andrea Doria.
September 29 through October 6 – a volcanic eruption in Italy creates Monte Nuovo.
October 28 – The first university of the New World, the Universidad Santo Tomás de Aquino, is founded.
Sucre, Bolivia, is founded under the name Ciudad de la Plata de la Nueva Toledo
Byland Abbey is dissolved.
Michelangelo starts work on the Piazza del Campidoglio (Capitoline Hill).
Bisham Abbey is dissolved.
The first in a decade-long series of severe famines and epidemics sweep central and southeastern China during the Ming Dynasty, made worse by a previous decision in 1527 to cut back on the intake of grain quotas for granaries.
In China, a tsunami floods over the seawall in Haiyan County of Zhejiang province, inundating the agricultural crop fields with saltwater and ruining many acres of crops. This drives up the price of foodstuffs and many are forced to live off of tree bark and weeds (as one Wang Wenlu stated in his writing of 1545).
Paracelsus visits Villach.
January 6 – Jane Dormer, English lady-in-waiting to Mary I (d. 1612)
January 10 – Louis of Nassau, Dutch general (d. 1574)
January 13 – Udai Singh of Marwar, Ruler of Marwar (d. 1595)
January 15 – Maeda Toshiie, Japanese samurai and warlord (d. 1599)
January 16 – John Frederick III, Duke of Saxony and nominal Duke of Saxe-Gotha (d. 1565)
February 23 – Dorothy Catherine of Brandenburg-Ansbach (d. 1604)
March 25 – Christopher Clavius, German mathematician and astronomer (d. 1612)
April 24 – Guglielmo Gonzaga, Duke of Mantua (d. 1587)
April 26 – Gian Paolo Lomazzo, Italian painter (d. 1600)
May 29 – Thomas Pounde, Jesuit lay brother (d. 1613)
June 30 – Bonaventura Vulcanius, Flemish Renaissance humanist (d. 1614)
July 8 – Alberto Bolognetti, Roman Catholic cardinal (d. 1585)
July 12 – Infanta Maria of Guimarães, Portuguese infanta (d. 1577)
August 30 – Caesar Baronius, Catholic cardinal (d. 1607)
September 21 – Lewis Mordaunt, 3rd Baron Mordaunt, English Member of Parliament (d. 1601)
Johan II of East Frisia, Count (d. 1591)
Joan Terès i Borrull, Viceroy of Catalonia (d. 1603)
October 2 – Saint Charles Borromeo, saint and cardinal of the Roman Catholic Church (d. 1584)
October 31 – Caesar Baronius, Italian cardinal and historian (d. 1607)
November 16 – Saint Turibius of Mongrovejo, Spanish Grand Inquisitioner, missionary Archbishop of Lima (d. 1606)
December 6 – Francesco Gonzaga, Catholic cardinal (d. 1566)
December 8 – Miklós Istvánffy, Hungarian politician (d. 1615)
December 10 – Giovanni Battista Guarini, Italian poet (d. 1612)
December 11 – Sigismund of Brandenburg, Archbishop of Magdeburg, Administrator of Halberstadt (d. 1566)
December 13 – Sigrid Sture, Swedish Governor (d. 1613)
December 19 – Jan Zborowski, Polish noble (d. 1603)
December 21 – Luigi d'Este, Catholic cardinal (d. 1586)
François de Bar, French scholar (d. 1606)
Diane de France, illegitimate daughter of Henry II of France (d. 1619)
Kitsuno, concubine of Japanese daimyo (d. 1566)
Ashikaga Yoshihide, Japanese shogun (d. 1568)
January 8 – Beatrice of Portugal, Duchess of Savoy (b. 1504)
February 12 – Albrecht Altdorfer, German painter (b. c. 1480)
April 3 – Elizabeth Boleyn, Countess of Wiltshire (b. 1480)
April 4 – Elena Glinskaya, Regent of Russia
May 8 – Edward Foxe, English churchman (b. 1496)
May 22 – John Forest, English Franciscan friar (martyred) (b. 1471)
June 30 – Charles II, Duke of Guelders (b. 1467)
July 8 – Diego de Almagro, Spanish conquistador (b. 1475)
September 14 – Henry III of Nassau-Breda, Baron of Breda (b. 1483)
October 20 – Francesco Maria I della Rovere, Duke of Urbino, condottiero (b. 1490)
November 22 – John Lambert, English Protestant martyr (burned at stake)
date unknown – Pierre Gringoire, French poet and playwright (b. 1475)
date unknown – Paganino Paganini, Italian publisher
Year 1538 (MDXXXVIII) was a common year starting on Tuesday (link will display the full calendar) of the Julian calendar.