The region was sparsely populated by indigenous Changos and Atacameños until massive Chilean immigration in conjunction with a saltpeter boom in the later 19th century.

In pre-Columbian times, the coastline was populated by nomadic fishing clans of Changos Indians, of which very little is known due to very limited contact with the Spanish conquerors.

Chile claimed that according to the Uti possidetis of the Spanish crown, the coastal region belong to them and their territory bordered directly with Peru.

Two of the largest and richest open pit mines in the world are located inland from Antofagasta: La Escondida and Chuquicamata.

[6] Most of the population lives on the coast in Antofagasta and Mejillones, or in Calama in the interior, the hub of the mining industry and the home of a large part of its work force.

In the late 19th and early 20th centuries, immigrant settlers also arrived from Europe (mainly Croatians, Italians, Spaniards, Greeks, English, French, and Portuguese peoples), from the Levant, and in smaller numbers from China, Japan, Korea, Peru and Bolivia.

It represents 53% of Chile's mining output, led by copper and followed by potassium nitrate, gold, iodine, and lithium, which means it could have had GDP per capita higher than Luxembourg had it had a large degree of autonomy.

The availability of infrastructure and services, due to the region's mining boom, together with its abundance of beautiful natural scenery, have opened vast prospects for the travel industry, both in the interior and on the coast.

Interesting tourist attractions include the small town of San Pedro de Atacama, once the center of the Atacameño culture, Atacama Salt Flat, the Valley of the Moon, the Quitor Pukará, the Puritama hot springs and the numerous astronomical observatories including the Very Large Telescope and ALMA.