The Natural and Moral History of the Indies, published in Seville in 1590, is the most famous work by Father José de Acosta (1540-1600) and one of the most important pieces of missionary literature. It has enjoyed widespread reception thanks to numerous reissues and translations, a true reflection of its quality. It offers not only an ample insight into the state of art of the sciences in the 16th century, but it also includes very interesting translation aspects. What stands out is a large lexicographic contribution of Americanisms followed by definitions and explanations that show the endless wealth of knowledge and experience of the author. When it comes to explaining the idiosyncratic features of the New World (from a European perspective, though with an indigenist filter), Acosta uses other translation processes as well. After contextualizing the work and establishing its characteristic structural features, the article analyses the translation aspects of the text.