Around A.D. 1100, many groups began to construct structures such as multi-room pueblos, more substantial than the pithouses and brush shelters used up to that time. Some societies, notably among the Hohokam and ancestral Puebloans, achieved greater degrees of social and political complexity, possibly based on individual differences in wealth, social status and political influence. These groups constructed towns that housed hundreds or even thousands of people. Late in the prehistoric period, changes in environmental conditions, social networks, or population size may have contributed to resource shortages and conflict. Many groups abandoned such areas as valleys and aggregated into larger, more defensible settlements in upland areas or remote canyons. Such settlements included pueblos on Perry Mesa that are now managed within the Agua Fria National Monument. There is evidence of warfare during this period. By A.D. 1450, many of these large settlements and some geographic areas were apparently abandoned as groups migrated to other regions such as the area now inhabited by the Hopi Tribe. It is possible that in some areas, people reverted to less intensive and more mobile subsistence practices and smaller settlements. Diseases introduced later by European immigrants may have caused dramatic declines in native populations.

Many modern tribes, including the Hopi and the O'odham, may be the descendants of the ancestral Puebloans, Mogollon and Hohokam. Archaeological and linguistic evidence indicate that other groups such as the Navajo, Apache and Paiute were later immigrants to Arizona, arriving sometime before the fifteenth century.

The Spanish arrived in Arizona in 1540 when the expedition of Francisco Vasquez de Coronado made its way north along the San Pedro River en route to Zuni. Other Spaniards followed, accompanied by missionaries sent by the Spanish Crown to pacify the native populations. Father Eusebio Francisco Kino traveled extensively between the San Pedro and Gila Rivers between 1691 and 1702, establishing missions and introducing European livestock and crops to the Indian rancherias. In 1775, Captain Juan Bautista de Anza led a colony of settlers to California along the Santa Cruz and Gila Rivers, passing by Painted Rocks. Anza's route is now a designated Millennium Trail managed in part by the BLM. On the eve of American Independence in 1776, Fathers Silvestre Velez de Escalante and Francisco Atanasio Dominguez were the first Europeans to traverse the Arizona Strip. That same year, construction began on the Presidio of Santa Cruz de Terrenate, now managed by BLM, to guard the northern border of New Spain.

In the mid-1820's, Anglo-American fur trappers, known as "mountain men," entered Arizona and began trapping the Gila River. One of the most famous was Jedediah Smith, who traveled down the Virgin River through the Arizona Strip, then down along the Colorado. Another was Kit Carson who was later hired to guide the U.S. Army. After the United States acquired what is now Arizona through the war with Mexico in 1848 and the Gadsden Purchase in 1854, another "army" of American explorers and surveyors descended on the Territory to survey the international boundary, mark wagon roads, scout possible routes for a transcontinental railroad, and determine the limits of navigation on the Colorado. The Butterfield Overland Mail stage began semiweekly service across Arizona in 1858, its route still traceable on BLM lands. The incursions of whites were understandably not welcomed by the Indians, and an average of twenty-one skirmishes between Indians and whites occurred each year from 1866 to 1875. Approximately three dozen military camps and forts were established and used in Arizona between 1865 and 1920.

Ranching has been an important part of Arizona's history since the 17th century when Spanish missionaries introduced cattle. Large Spanish, and later Mexican, land grant ranches operated in the southern part of the State. Two 1827 Mexican land grants, the San Juan de las Boquillas y Nogales grant and the San Rafael del Valle grant, were later acquired by the BLM and designated by Congress as the San Pedro Riparian National Conservation Area. One of the most important ranches at the end of the 19th century was Walter Vail's Empire Ranch, controlling nearly a thousand square miles of range stretching from the Mexican border to the Rincon Mountains. Its adobe headquarters remain today as one of BLM's most important historic properties.

After the gold rush waned in California, miners came east to prospect in Arizona, finding rich strikes of silver and gold. Boom times began, bringing more people to the Territory. The population of Arizona doubled between 1860 and 1864, then doubled again by 1870. By 1880, one out of five male workers in the Territory was a miner. Silver dominated production in the beginning, but by 1888, copper took its place as the mainstay of Arizona's economy. Settlement followed the development of mineral deposits, bringing residents and towns to Arizona's southern, central and western deserts. Copper mining has continued to play a vital role in the State's history. By 1981, Arizona ranked first among the United States in production of copper.