The Atacama Desert is a biodiversity hotspot of neo-endemic radiation, where long-term aridity and complex physiographic processes create a unique environmental setting. Current species assemblages are mainly concentrated in highly patchy loma formations, and plant populations occurring in these are often geographically isolated from each other. Despite a general consensus on long-term aridity in the Atacama, climatological and geological evidence points to repeated climate change, making the Atacama Desert an ideal system for studying population genetic processes in highly unstable habitats. We are analyzing the genetic structure within and between populations ofHuidobria fruticosa, a paleo-endemic lineage of the Atacama Desert, to shed new light on its biogeographic history and broaden our understanding of the evolution of life in extreme aridity, as well as plant evolution in response to a changing environment. To do this, we analyzed SNP data from genotyping-by-sequencing of 354 individuals from 21 populations. Our results suggest that, despite being an ancient lineage, the current population structure ofHuidobria fruticosaonly reflects changing abiotic conditions over the last 2 million years. We therefore conclude that the present distribution, together with the evolutionary processes documented here, is the result of climatic fluctuations and prolonged periods of hyperaridity during the Pleistocene. Building on this understanding, our findings contribute to a global narrative that highlights the complex interplay between climate change and evolutionary dynamics, and emphasize the importance of deserts as living laboratories for deciphering how species have historically adapted to some of the most extreme habitats on Earth.