One of the signature historical phenomena of the past 500 years has been the global expansion of European societies and their trans-Atlantic offshoots. The mercantile networks, commercial systems, and empires of conquest and colonization that formed the political and economic framework of that expansion involved the discovery and extraction of new mineral and agricultural resources, the establishment of new infrastructures of transport and communication, and the forcible relocation of millions of people. Another key component was the Columbian Exchange, the multiple transfers of people, animals, plants, and microbes that began even before Columbus, gathered pace after 1492, and were further fuelled as European settlement advanced into Africa, Australasia, and the Indian and Pacific Oceans. Donkeys evolved in the Old World and were confined there until the Columbian Exchange was underway. This chapter explores the introduction of the donkey and the mule to the Americas and, more briefly, to southern Africa and Australia. In keeping with my emphasis on seeking archaeological evidence with which to illuminate the donkey’s story, I omit other aspects of its expansion, such as the trade in animals to French plantations on the Indian Ocean islands of Réunion and Mauritius or, on a much greater scale, India to meet the demands of the British Raj. These examples nevertheless reinforce the argument that mules and donkeys were instrumental in creating and maintaining the structures of economic and political power that Europeans and Euro- Americans wielded in many parts of the globe. From Brazil to the United States, Mexico to Bolivia, Australia to South Africa, they helped directly in processing precious metals and were pivotal in moving gold and silver from mines to centres of consumption. At the same time, they aided the colonization of vast new interiors devoid of navigable rivers, maintained communications over terrain too rugged for wheeled vehicles to pose serious competition, and powered new forms of farming. Their contributions to agriculture and transport were well received by many of the societies that Europeans conquered and their mestizo descendants. However, they also provided opportunities for other Native communities to maintain a degree of independence and identity at and beyond the margins of the European-dominated world.