In the sixteenth century, Portugal overwhelmingly dominated European trade with sub-Saharan Africa and the East Indies. West Africa, because of its proximity to Brazil, had particular commercial importance. Slaves, needed for sugar production in Brazil, were shipped from the west coast of Africa in large numbers, though they were also captured and sent to the Americas from Portuguese-ruled areas of the coast of East Africa. Among the traders who became involved in this human trafficking were New Christians, who in Portuguese Africa were safe from inquisitorial persecution. However, most of the traders came for short periods before moving elsewhere, since the Portuguese did not regard the coast of Africa as a desirable place for settlement.

The situation in Portuguese Asia was different. There, Portuguese subjects settled permanently at important trading outposts. A few conversos and practicing Jews settled in Ormuz in the Persian Gulf. But they were confronted by an actively missionizing Jesuit presence, and this, along with the comparatively unattractive conditions of life, kept their numbers small. Our best knowledge of the New Christian presence comes from the Inquisition records of the Goa tribunal, which was established in 1560 as a response to complaints about New Christian judaizing. Among the East Indian New Christians prosecuted for heresy, a number were burned at the stake at Goan autos-da-fé.

Within the Portuguese East Indian sphere, it was only in Cochin on the Malabar coast that a long-established Jewish community continued to thrive. It was able to do so because it enjoyed the protection of the rajah of Cochin. Among the newcomers who settled there in the early sixteenth century were Jews and New Christians from Spain and Portugal.

Once Portuguese hegemony in the East Indies was challenged by the Netherlands, England, and France in the seventeenth century, a greater opening was created for Jewish settlement. Still, it was only in Cochin, after the Dutch captured it in 1663, that a Sephardic Jewish community thrived and developed strong ties to the Portuguese-Jewish diaspora. In 1686, the Portuguese-Jewish community of Amsterdam sent a delegation to Cochin, collecting information about the community and bringing to it Hebrew books produced by the Amsterdam presses. The strong tie between the Amsterdam Jews and the Jews of Cochin was maintained until Dutch rule came to an end in Cochin in 1795.