Vasco da Gama, setting out in April 1524 with a fleet of fourteen ships, had taken as his flagship the famous large carrack Santa Catarina do Monte Sinai on her last journey to India, along with two of his sons, Estêvão and Paulo.

After a troubled journey (four or five of the ships were lost en route), he had arrived in India in September.

Vasco da Gama had immediately invoked his high viceregent powers to impose a new order in Portuguese India, replacing all the old officials with his own appointments, but Gama had contracted malaria not long after arriving, and died in the city of Cochin on Christmas Eve in 1524, three months after his arrival.

As per royal instructions, da Gama is succeeded as governor of India by one the captains who had come with him, Henrique de Menezes (no relation to Duarte).

Vasco's sons Estêvão and Paulo immediately lose their posts and will join the returning fleet of early 1525 (along with the dismissed Duarte de Menezes and Luís de Menezes).

Vasco da Gama's body is first buried at St. Francis Church, which is located at Fort Kochi in the city of Kochi, but his remains will be returned to Portugal in 1539 and his body re-interred in Vidigueira in a casket decorated with gold and jewels.