From the early 15th century, the nautical school of Henry the Navigator and been extending Portuguese knowledge of the coast of Africa.

From the 1460s, the goal had become one of rounding that continent's southern extremity and gaining direct access to the riches of India, mainly black pepper and other spices. Born in Sines, Portugal, da Gama was just shy of thirty years old as these long-term plans were coming to fruition.

Bartolomeu Dias had returned from rounding the Cape of Good Hope and exploring as far as the Fish River in modern-day South Africa, while from India Pero da Covilhã had explored south for some of the distance intervening between Dias' explorations and the subcontinent. It remained only for the two segments to be joined into one voyage. This task was given to Da Gama's father, Estêvão da Gama, but he died before he could begin.

Vasco was then given the job on the strength of his work for the Portuguese crown along the Gold Coast of Africa. On July 8, 1497 four ships (the São Gabriel, the São Rafael, the Berrio, and a storage ship of unknown name) left Lisbon and the voyage began. 

By December 16 they had passed the Fish River and continued on into waters unknown to Europeans. With Christmas pending they gave the coast they were passing the name Natal (Christmas in Portuguese), which it retains to this day.

By January they had reached modern-day Mozambique, Arab-controlled territory on the East African coast that was part of the Indian Ocean's network of trade. Having got that far, da Gama was able to employ a pilot at Malindi, who brought the expedition the rest of the way to Calicut (the exact Malayalam name is Kozhikode) on the southwest coast of India on May 20, 1498.

Da Gama assaulted and exacted tribute from the East African Arabian port of Kilwa, which had been one of those involved with frustrating the Portuguese; he played privateer amongst Arab merchant ships; and then finally smashed a Calicut fleet of twenty-nine ships and essentially conquered that port city.

In return for peace, he received valuable trade concessions and a vast quantity of plunder that put him in extremely good favor with the Portuguese crown.

Returning to Portugal, he was made Count Vidigueira out of lands that had previously belonged to the royal Bragança family.

Having acquired a fearsome reputation as a "fixer" of problems that arose in India, he was sent to the subcontinent once more in 1524. The intention was that he was to replace the incompetent Eduardo de Menezes as viceroy of the Portuguese possessions, but he died not long after arriving in Calicut. After burial for some time in India, his remains were returned to Portugal in 1539 and re-interred in Vidigueira.

As much as anyone after Henry the Navigator, da Gama was responsible for Portugal's success as an early colonizing power. Besides the first voyage itself,it was his astute mix of politics and war on the other side of the world that placed Portugal in a prominent position in the Indian Ocean trade.