The year 1580 in science and technology included many events, some of which are listed here.

• The Constantinople Observatory of Taqi ad-Din is destroyed by Sultan Selim II.

• September 26 – Francis Drake in the Golden Hind sails into Plymouth having completed the second circumnavigation of the world, westabout, begun in 1577.

• Severe outbreak of smallpox in Venezuela: it strikes the Caracas and other Indians in the North and greatly weakens Indian resistance to the Spanish colonizing of the region.^[1]

• April 6 – Dover Straits earthquake.^[2]

• January 12 – Jan Baptist van Helmont, Flemish chemist (died 1644)^[3]
• December 1 – Nicolas-Claude Fabri de Peiresc, French astronomer (died 1637)
• Peter Crüger, German polymath (died 1639)
• Willebrord Snellius, Dutch mathematician and physicist who devised the basic law of refraction, Snell's law (died 1626)

• May 3 – Thomas Tusser, English chorister and agriculturalist (born c. 1524)
• September 15 – Friedrich Risner, German mathematician (born c. 1533)
• Giovanni Filippo Ingrassia, Sicilian anatomist (born 1510).