This interdisciplinary study represents an approximation towards understanding how regional human cultural systems may have been affected by climate change in the northernmost Chilean Altiplano (>3600 m) over the last ca. 11 500 cal a BP. We compare the archaeological record from Hakenasa cave with the lake record from Lago Chungará sediment cores, located 50 km to the south. By integrating both of these archives in conjunction with regional palaeoclimate and archaeological data, we provide new evidence for the role of changing environmental and climatic conditions in human settlement patterns. The first human occupation of the entire Altiplano occurs at Hakenasa and is dated to 9980 ± 40 14C a BP (11 265–11 619 cal. a BP), and took place under wetter regional climate conditions. An archaeologically sterile deposit occurs at Hakenasa between 7870 and 6890 cal. a BP. Constituted by sands and gravels, these sediments are interpreted as a flood event. This time period is synchronous with alternating short dry and wet events recorded in the Lake Chungará sedimentary sequence. Human activity resumes and increases in importance at Hakenasa by ca. 6000 cal. a BP. This corresponds to wetter conditions indicated by the Chungará record. Even though the lake record indicates intense volcanic activity over the last 6000 cal. a BP, this had little or no impact on the human population present at Hakenasa. This study shows that even in this extreme environment human settlement patterns do not always respond in a linear fashion to environmental change. Copyright © 2008 John Wiley & Sons, Ltd.