He studied mathematics under Pedro Nunes, along with Luis, Duke of Beja, son of King Manuel I of Portugal, with whom he formed a lifelong friendship.

His estate of Penha Verde, in Sintra, contains the two famous black stones of Cambay, retrieved by de Castro and his son.

Seconded by his sons (one of whom, Fernão, was killed) and by João Mascarenhas, de Castro overthrew Mahmud, King of Gujarat, and defeated the army of the Adil Khan.

[3] After the victory of his Armada in the relief of Diu, he asked the king to not prolong his term of office beyond the ordinary three years and to allow him to return to the Sintra Mountains in Portugal.

After his victory over Mahmud and the Adil Khan, de Castro rebuilt Diu with the money received from the citizens of Goa.

When de Castro attempted to determine the latitude of Mozambique on 5 August 1538, he noted the deviation of the needle 128 years before Guillaume Dennis (1666) of Nieppe, who is normally credited with this discovery.

He discovered spatial variations of declination in the bay of Bombay (near Bassein), which he attributed to the disturbing effects of underwater rock masses.

[citation needed] In the 1890s, G. Hellman, quoted by Chapman and Bartels (1940), considered de Castro to be the most important representative of scientific maritime investigations of the time, and the method he tested was universally introduced on ships and used until the end of the sixteenth century.