For centuries, Asian peoples migrated to the Americas by land and sea. They developed an astonishing array of cultures and societies, from small hunting-and-gathering bands to complex empires. In the fourteenth and fifteenth centuries, extensive commercial and political networks existed among the Mississippians, the Aztecs, and the Incas, although only the latter two continued to thrive by the late 1400s. In southern Europe, too, during the fifteenth century, economic, cultural, and political advances fueled interest in long-distance trade and exploration. Italy and Portugal led these efforts, but their monopoly of trade routes across the Mediterranean and around Africa to Asia forced Spain to look west in hopes of gaining access to China and the Indies. In doing so, the Spanish unexpectedly came into contact with the Americas.

When Spanish explorers happened upon Caribbean islands and the nearby mainland, they created contacts between populations that would be dramatically transformed in a matter of decades. While native residents of the Americas were sometimes eager to trade with the newcomers and to form alliances against their traditional enemies, they fought against those they considered invaders. Yet some of the most significant invaders—plants, pigs, and especially germs—were impossible to defend against. Even Europeans seeking peaceful relations with native inhabitants or bent on conversion rather than conquest brought diseases that devastated local populations and plants and animals that transformed their landscape, diet, and traditional ways of life.

Waldseemüller died in 1521 or 1522, so he did not see the most dramatic changes that his remarkably accurate maps inspired. Malintzin, however, experienced those changes firsthand. She watched as disease ravaged not only rural villages but even the capital city of Tenochtitlán. She encountered horses, pigs, attack dogs, and other European animals. She ate the foods and wore the clothes that her Spanish captors provided. In 1522, Malintzin gave birth to Cortés’s son; two years later, she served as interpreter when he ventured north to conquer more territory. In 1526 or 1527, however, she married a Spanish soldier, Juan Jaramillo, settled in Mexico City, and bore two more children. As more and more Spaniards, including the first women, settled in New Spain, Malintzin realized that her children would grow up in a world very different from the one in which she was raised.

From the 1490s to the 1580s, the most dramatic and devastating changes for native peoples occurred in Mexico, the West Indies, Central America, and South America. But events there also presaged what would happen throughout the Americas. As Spanish conquistadors ventured into Florida and the Gulf Coast and French and English explorers sought to gain footholds along the Atlantic seaboard, they carried sufficient germs, seeds, and animals to transform native societies even before Europeans established permanent settlements in North America.

In the century to come, contacts and conflicts between native peoples and Europeans escalated as France, England, and the Netherlands joined Spain in colonizing North America. Conflicts among European nations also multiplied as they struggled to control land, labor, and trade. Moreover, as Indian populations died out in some regions and fended off conquest in others, Europeans turned increasingly to the trade in Africans to provide the labor to produce enormously profitable items like sugar, coffee, and tobacco.