Year 1480 (MCDLXXX) was a leap year starting on Saturday of the Julian calendar.

• March 6 – Treaty of Toledo: Ferdinand and Isabella of Spain recognize the African conquests of Afonso V of Portugal, and he cedes the Canary Islands to Spain (see Treaty of Alcáçovas).^[1]
• July 28
  • Mehmed II fails in his attempt to capture Rhodes from the Knights of Rhodes.
  • An Ottoman army lands near Otranto, Italy. Pope Sixtus IV calls for a crusade to drive it away.
• September 27 – Consorts and co-rulers Ferdinand II of Aragon and Isabella I of Castile initiate the Spanish Inquisition (looking for heretics and unconverted Jews).
• October – Great Stand on the Ugra River: Muscovy becomes independent from the Golden Horde. The Theotokos of Vladimir icon is credited with saving Moscow.

• The Lighthouse of Alexandria's final remains disappear when Qaitbay, Sultan of Egypt, builds the Citadel of Qaitbay on its site.
• Magdalen College School, Oxford, is established by William Waynflete.

• January 10 – Margaret of Austria, Regent of the Netherlands (d. 1530)
• February 12 – Frederick II of Legnica, Duke of Legnica from 1488 (until 1495 and 1505 with his brothers) (d. 1547)
• February 13 – Girolamo Aleandro, Italian Catholic cardinal (d. 1542)
• April 10 – Philibert II, Duke of Savoy (d. 1504)
• April 18 – Lucrezia Borgia, Duchess of Ferrara (d. 1519)^[2]
• June 1 – Tiedemann Giese, Catholic bishop from Danzig (Gdańsk) in Poland (d. 1550)
• July 5 – Philip of the Palatinate, Bishop of Freising and Naumburg (d. 1541)
• November 10 – Bridget of York, English nun (d. 1517)^[3]
• October – Saint Cajetan, founder of the Theatines (d. 1547)
• date unknown
  • Vannoccio Biringuccio, Italian metallurgist (d. 1539)
  • Claude Garamond, French publisher (d. 1561)
  • Giovanni Guidiccioni, Italian poet (d. 1541)
  • Ferdinand Magellan, Portuguese explorer (d. 1521)
  • Jerzy Radziwiłł, Polish nobleman (d. 1541)
  • Gazi Husrev-beg, Ottoman statesmen (d. 1541)
  • Palma il Vecchio, Italian painter (d. 1528)
• probable
  • Arasibo, Taino Cacique
  • Hans Baldung, German painter (d. 1545)
  • Matteo Bandello, Italian novelist (d. 1562)
  • Johann Georg Faust, German alchemist (d. 1540)
  • Anna Taskomakare, Swedish merchant craftswoman and estate owner (d. after 1528)
  • Jumacao, Taino Cacique
  • Conn O'Neill, 1st Earl of Tyrone (d. 1559)
  • Marcantonio Raimondi, Italian engraver (d. c. 1534)
  • Elizabeth Boleyn, Countess of Wiltshire (d. 1538)

• January 5 – Jakobus, nobleman from Lichtenberg in the northern part of Alsace (b. 1416)
• April 14 – Thomas de Spens, Scottish statesman and prelate (b. c. 1415)
• May 10 – Philipp I, Count of Hanau-Lichtenberg (1458–1480) (b. 1417)
• May 19 – Jan Długosz, Polish historian (b. 1415)
• May 25 – William III, Count of Henneberg-Schleusingen (b. 1434)
• June 6 – Vecchietta, Italian painter, sculptor and architect (b. c. 1410)^[4]
• July 6 – Antonio Squarcialupi, Italian composer (b. 1416)
• July 10 – René of Anjou, king of Naples (b. 1409)^[5]
• July 15 – John III, Count of Nassau-Weilburg, German nobleman (b. 1441)
• July 26 – Ruprecht of the Palatinate, Archbishop and Prince Elector of Cologne (b. 1427)
• September 1 – Ulrich V, Count of Württemberg (b. 1413)
• October 4 – Jakub of Sienno, medieval Bishop Kraków in the years 1461–1463 (b. 1413)
• October 18 – Uhwudong, Korean dancer (b. 1440)
• November 20 – Eleanor of Scotland, Scottish princess (b. 1433)
• November 29 – Frederick I, Count Palatine of Simmern (b. 1417)
• December 14 – Niccolò Perotti, Italian humanist scholar (b. 1429)
• date unknown
  • Nicolas Jenson, French engraver (b. 1420)
  • Tristão Vaz Teixeira, Portuguese explorer (b. c. 1395)
  • Antonio Vivarini, Italian painter (b. c. 1440)
  • Joana de Castre, Catalan noble (b. 1430)