The Bolivian highlands, permanently settled at least for 21,000 years, were part and parcel of the culture of Andean South America prior to the arrival of the Spaniards. The records through fragmentary suggest that agriculture started by 3000 B.C. and metal production, especially copper, began 1,500 years later.

By 600 B.C., the first great Andean empire had come into being on the high plateau amid the mountains known as the Altiplano. This empire, the Tiahuanacan, was centred nearby to the southeastern side of Lake Titicaca and included urban centers around the lake, as well as enclaves in dissimilar ecological zones from the eastern valleys to the Pacific Coast. Tiahuanaco was an important center of trade and religion, and the influence of its culture reached far beyond the borders of present-day Bolivia. Actually, the Tiahuanacan Empire was established through colonization rather than through conquest.

The collapse of Tiahuanacan power led to the rise of seven regional kingdoms of the Aymara, the most dominant states located in the densely populated area around Lake Titicaca. The Aymara, a belligerent people who used to live in fortified hilltop towns, exhibited an extraordinary ability to adapt to the unique climatic conditions of the area and augmented their food supply through irrigation and the process of drying and freezing crops. Basic social unit these people was the ayllu, a clan or kinship group that organized work and distributed land among its members. The Aymara completely subjugated the Uru, another major ethnic group in the pre-Columbian southern Andes, Uru might have preceded the Aymara in the region though. Uru were poor fishermen and landless workers.

The Aymara, nevertheless, failed to contain the expansion of the Quechua, the third major ethnic group. After the breakdown of the Tiahuanacan Empire, a Quechua-speaking state emerged in the area around Cuzco (in present-day Peru). In the early fifteenth century, the Quechua, known also as the Incas, were the most influential group in the northern highlands. As the Aymara kingdoms in the south weakened in the second half of the fifteenth century, the Incas set out to conquer them.

The Bolivian highlands was called Kollasuyo. It was a densely populated area with great economic and mineral wealth and was one of the four administrative units of the Inca Empire. The highest official of the Kollasuyo was answerable only to the Inca (the emperor) and supervised a group of provincial governors, who in turn controlled members of the Aymara nobility. Under mita, a draft system, the Incas forced local Indians residing in the Kollasuyo to work in the mines or on construction projects or to serve in the armies, compensating them reasonably for their labor. Despite their objective of extreme centralization, the Incas did not fundamentally alter the organization of the Aymara kingdoms, which remained very much autonomous. Many local chiefs retained many of their former powers and were, in general, reinforced by Inca authority. They also managed to retain their culture, their local religion, and their language.

In 1470, several Aymara kingdoms revolted against Inca rule. The Incas completely crushed two states and pacified the area by sending mitimas. The Incas were unsuccessful in conquering the nomadic tribes in the eastern Bolivian lowlands though. The ruins of Incan fortresses there are evidence of this failure and suggest that the Incas could subdue only those cultures that were primarily based on agriculture. Thus, the Indian groups of the eastern two-thirds of Bolivia could preserve their ways of life to a great extent, even after the Spanish conquest.

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