The year 1521 in science and technology included many events, some of which are listed here.

• January – Antonio Pigafetta, sailing with Magellan's expedition, observes Magellanic Clouds.

• Francisco de Gordillo explores the Atlantic coast up to South Carolina.^[1]
• March 6 – Ferdinand Magellan discovers Guam in the Mariana Islands.
• March 16 – Magellan reaches the Philippines.
• April 7 – Magellan arrives at Cebu Island.
• November 8 – Magellan's expedition, now led by Juan Sebastián Elcano, arrives in the Maluku Islands.

• Jacopo Berengario da Carpi publishes Commentaria cum amplissimus additionibus super anatomiam Mundini in Bologna, containing the first printed anatomical illustrations taken from nature and including observation of the vermiform appendix.

• Valentin Mennher, German mathematician (d. c.1571).
• approx. date – Richard Chancellor, English Arctic explorer (drowned 1556).

• April 27 – Ferdinand Magellan, Portuguese explorer (born c.1480) (killed in the Philippines).
• July 8 – Jorge Álvares, Portuguese explorer.
• Francisco Serrão, Portuguese explorer.