Determining the existence and nature of regime shifts in socio-environmental systems is key to anticipating their dynamics. However, such transitions are difficult to study, among other reasons, because environmental responses tend to be slow and lagged, and monitoring data rarely capture multiple transitions. Here we will focus on the issue of regime shifts in the high-altitude tropical Andes, where during millennia lakes have been instrumental in sustaining human communities that have altered, in turn, the quantity and quality of fresh water stored in these valuable ecosystems. Our overarching question is: What insights do abrupt transitions in the palaeoenvironmental record provide about the critical stressors and ecosystem response that give rise to the current state of Andean socio-ecological systems? This question will be addressed by studying a unique, 3000-year record of an Ecuadorean lake-catchment system as a model for tropical Andean socio-environmental systems. We will identify feedbacks between proxies for human activity in the catchment (deforestation, damming, eutrophication), and lake ecosystem responses, using diatom community time-series data to identify regime shifts. Subsequently, using a space-for-time substitution approach we will look for stable and/or transient lakes in a natural-rural gradient across the Andes. In that case, we will use spatial and temporal data sets of multiple stressors over the last decades to predict which lakes are about to experience (or have experienced) a regime shift. Our approach is novel because contrasting with most resilience research, our millennia-scale analysis should show multiple transitions between ‘basins of attraction’. Additionally, we will develop a robust quantitative framework that allows combining data at two disparate temporal scales (palaeoenvironmental and contemporary). This framework will be readily transferable to systems with similar time-series data. Overall, our project will contribute methods and findings that should advance our understanding of regime shifts in complex socio-ecological systems.