The initial policy instituted by the Spanish conquistadores in Mexico was to play Indian peoples against each other in order to conquer the Aztecs, by far the dominant political force in the region. When Hernando Cortes defeated the Aztecs in 1521, he instituted the encomienda system by which encomendaros, or regional governors, exacted tribute in the form of silver and other precious metals from subject Indians. The encomendaros were also responsible for the Christianization of the Indians under their supervision, and while the encomienda system, which was rife with abuses, would only survive a short time, forcibily evangelizing indigenous peoples was a signature component of Spanish Indian policy.

Portuguese colonists also emphasized conversion, but rather than establishing a metal-extraction based encomienda system, they used native labor to work on sugar plantations. Due to immense losses among natives on these plantations, Portuguese plantation owners quickly turned to African slaves for labor.

French colonists in North America never settled in the numbers that their British counterparts did, and for this reason, usually dealt with native peoples from a position of numerical weakness. As a consequence, they emphasized fair treatment of natives, and appealing to mutually beneficial policies. They also emphasized Christianity, importing large numbers of Jesuits, but trade, and the establishment of strategic alliances with native peoples were the main emphases of French policy.

English colonists, with some notable exceptions, showed little interest in converting native peoples. Their approaches to Indians often led to violent wars, including the Pequot War in New England, Powhatan's War in the Chesapeake, and the Tuscarora and Yamassee Wars in the Carolinas. English settlers were notably landhungry, and this made cooperative approaches to dealing with natives less and less palatable as colonists arrived in increasing numbers. English colonies did cultivate alliances and engage in large-scale trade, as in the beaver trade in the North and the deerskin and Indian slave trade in the southern colonies.