Europeans called the Americas “the New World.” But for the millions of Native Americans they encountered, it was anything but. Humans have lived in the Americas for over ten thousand years. Dynamic and diverse, they spoke hundreds of languages and created thousands of distinct cultures. Native Americans built settled communities and followed seasonal migration patterns, maintained peace through alliances and warred with their neighbors, and developed self-sufficient economies and maintained vast trade networks. They cultivated distinct art forms and spiritual values. Kinship ties knit their communities together. But the arrival of Europeans and the resulting global exchange of people, animals, plants, and microbes—what scholars benignly call the Columbian Exchange—bridged more than ten thousand years of geographic separation, inaugurated centuries of violence, unleashed the greatest biological terror the world had ever seen, and revolutionized the history of the world. It began one of the most consequential developments in all of human history and the first chapter in the long American yawp.