This work analyzes the processes of change in the pre-Hispanic human occupations (ca. 10000-500 BP) in the highlands of the Northwestern Argentina (south-central Andes). Specifically, archaeological studies in a high altitude desert called “Puna” are presented. It is an arid environment, characterized by a segmentation of productive spaces into patches. In particular, the archaeological evidence analyzed comes from the Alero Cuevas, Abrigo Pozo Cavado, Cueva Inca Viejo and Abra de Minas sites, located in the Puna of the Province of Salta, Argentina. These sites contain diverse indicators linked to changes in human occupations throughout the Holocene. From different lines of evidence such as the archaeofaunal record, lithic material and rock art, among others, processes such as the domestication of camelids, the consolidation of herding strategies, the llama caravans and the impact of the Incas in the region are discussed. The results of the archaeological studies allowed me to point out notable changes from an economy based on hunting-gathering to the predominance of herding strategies. Likewise, the archaeological record indicates the transmission of cultural information and the circulation of diverse resources on broad scales. During the late Holocene, these interaction processes were mainly linked to llama caravans. Another relevant process to highlight here is related to the expansion of the Inca Empire in some sectors of the highlands. This expansion produced an effective and symbolic appropriation of productive spaces and certain economic practices (e.g. mining) and rituals were intensified. In summary, the different indicators analyzed constitute a contribution to the study of adaptation strategies of human groups in environments characterized as high altitude deserts on a long-term chronological scale.