1539 (MDXXXIX) was a common year starting on Wednesday of the Julian calendar, the 1539th year of the Common Era (CE) and Anno Domini (AD) designations, the 539th year of the 2nd millennium, the 39th year of the 16th century, and the 10th and last year of the 1530s decade. As of the start of 1539, the Gregorian calendar was 10 days ahead of the Julian calendar, which was the dominant calendar of the time.

• May 30 – In Florida, Hernando de Soto lands at Tampa Bay with 600 soldiers with the goal to find gold.
• Hernando de Soto introduces Pigs into North America
• May – 6 Articles Statute of English Parliament, important in the English Reformation"
• September 4 – Henry VIII contracts to marry Anne of Cleves
• Lutheranism is forcefully introduced to Iceland, despite the opposition of Bishop Jon Aresson.
• The town of Shuya was founded

• November 1 – Pierre Pithou, French lawyer and scholar (died 1596)
• December 5 – Fausto Paolo Sozzini, theologian (died 1604)
• Luis Carvajal y de la Cueva, Portuguese Jewish explorer (died 1590)
• Georg Friedrich, Margrave of Brandenburg-Ansbach (died 1603)
• Catherine Grey, Countess of Hertford (died 1568)
• Hasegawa Tohaku, Japanese painter (died 1610)
• Ikeda Katsumasa, Japanese military commander (died 1578)
• Laurence Tomson, Calvinist (died 1608)

• February 6 – John III, Duke of Cleves, born 3 August 1491
• March 12 – Thomas Boleyn, 1st Earl of Wiltshire, diplomat, politician, and father of Anne Boleyn (born 1477)
• May 7 – Guru Nanak, founder of Sikhism (born 1469)
• May 7 – Ottaviano Petrucci, Italian printer (born 1466)
• July 5 – St. Anthony Maria Zaccaria, founder of the Barnabite Order (born 1502)
• September 8 – John Stokesley, English prelate (born 1475)
• James Beaton, Scottish church leader
• Vannoccio Biringuccio, Italian metallurgist (born 1480)
• Hugh Cook Faringdon, Abbot of Reading
• George, Duke of Saxony (born 1471)
• Symeon Iwanowicz Trubczewski, governor of Kostroma
• Isabella d'Este, "First Lady of the Renaissance" (born 1474)