1580 (MDLXXX) was a leap year starting on Friday in the Julian calendar.

• March 1 – Michel de Montaigne signs the preface to his most significant work, Essays. They are published later the same year.
• June 11 – Juan de Garay founds Buenos Aires.
• June 25 – Publication of the Book of Concord, a collection of Lutheran confessional documents.
• July 12 – Publication of the Ostrog Bible, the first complete printed Bible in a Slavic language.
• September 26 – Sir Francis Drake circumnavigated the globe
• Portugal loses independence to Spain following the death without heirs of king Henry of Portugal. The Habsburg rule would last until 1640.
• Yermak entered Siberia with a band of 1636 men. Russia begins the conquest of Siberia.
• Khorasan Wars were fought between Abbas the Great and his father king Mohammed Khodabandeh.