His proposal to sail to the East Indies by a westerly route was accepted and he set off in 1519. He sailed through what became named The Straits of Magellan a channel that runs for 600 km between the southern tip of South America and Tierra del Fuego an archipelago off the coast to the south. Having passed through the treacherous waters around the tip of South America he crossed the Pacific Ocean, and finally reached the Philippines in 1521.

Unfortunately he was killed in battle with the natives and died in the Philippines, leaving his companions to complete the voyage back to Europe. However he and his Malay slave Enrique de Malacca were the first circumnavigators of the globe since they had sailed from the Philippines to Europe before they started Magellan's final voyage.