Abstract In this article, we present the first and only documented source of turquoise exploited in Northwest Argentina (NOA) from the Late Prehispanic and Inca periods (ca. 900–1532 CE). The evidence for turquoise mining comes from Cueva Inca Viejo, an archaeological site located in the highlands of Province of Salta. Turquoise is a valuable mineral that has been exploited for millennia in the Andean region. Until now, there was no evidence for Prehispanic sources of this material being exploited in Northern Argentina. Due to this, all the turquoise found at Argentine archaeological sites was interpreted as allochthonous. The evidence presented here contributes to discuss this issue at a regional scale. Primarily, we analyse and discuss the role played by Cueva Inca Viejo in the mining and use of this mineral, and its links with macro-regional interaction processes and ritual practices. Physicochemical analysis (SEM-EDS and XRD) allowed us to identify turquoise from the cave wall, and from the archaeological layers. Likewise, we found stone hammers, the most important artefacts closely associated to Prehispanic mining. Among the archaeological materials recovered in Cueva Inca Viejo, it is important to highlight the rock-art with representations of llama caravans and anthropomorphic figures, as well as the discovery of feathers and cebil seeds (Anadenanthera colubrina) in archaeological contexts, both originary from the lowlands. We conclude that the expansion of the Inca Empire in the area was linked to the mining and the control of ritual activity. In this regard, we highlight the presence of a ceremonial structure with stairs, located outside the entrance of Cueva Inca Viejo. Our results show that there was a narrow relationship between mining, macro-regional interactions and ritual, at least, from the Late pre-Inca Period through to Inca expansion in the region.