The high tropical Andes are rapidly changing due to climate change, leading to strong biotic community, ecosystem, and landscape transformations. While a wealth of glacier, water resource, and ecosystem-related research exists, an integrated perspective on the drivers and processes of glacier, landscape, and biota dynamics is currently missing. Here, we address this gap by presenting an interdisciplinary review that analyzes past, current, and potential future evidence on climate and glacier driven changes in landscape, ecosystem and biota at different spatial scales. We first review documented glacier changes and landscape evolution over past decades to millennia and analyze projected future glacier shrinkage until 2100 for two case studies in the tropical Andes. The effects of climate and glacier change on high Andean biota are then examined from paleoecological research and comparative gradient analyses to chronosequence and diachronic studies of vegetation dynamics. Our analysis indicates major twenty-first century landscape transformations with important socioecological implications which can be grouped into (i) formation of new lakes and drying of existing lakes as glaciers recede, (ii) alteration of hydrological dynamics in glacier-fed streams and high Andean wetlands, resulting in community composition changes, (iii) upward shifts of species and formation of new communities in deglaciated forefronts,(iv) potential loss of wetland ecosystems, and (v) eventual loss of alpine biota. We advocate strengthening an interdisciplinary research agenda with a strong policy formulation link that enables enhanced cross-sectorial cooperation and knowledge sharing, capacity building of relevant stakeholders, and a more active participation of both government agencies and social organizations.