We use remote sensing to enhance the interpretation of the first baseline dataset of hydrologic, isotopic and hydrochemical variables spanning 620 km of the upper Marañón River, in Andean Peru, from the steep alpine canyons to the lower lying jungle. Remote, data-scarce river systems are under increased hydropower development pressure to meet rising energy demands. The upstream-downstream river continuum, which serves as a conduit for resource exchange across ecosystems, is at risk, potentially endangering the people, environments, and economies that rely on river resources. The Marañón River, one of the final free-flowing headwater connections between the Andes and the Amazon, is the subject of myriad large-scale hydropower proposals. Due to challenging access, environmental data are scarce in the upper Marañón, limiting our ability to do system-wide river basin planning. We capture key processes and transitions in the context of hydropower development. Two hydrologic regimes control the Marañón dry-season flow: in the higher-elevation upper reaches, a substantial baseflow is fed by groundwater recharged from wet season rains, in contrast to the lower reaches where the mainstem discharge is controlled by rain-fed tributaries that receive rain from lowland Amazon moisture systems. Sustainability of the upper corridor’s dry-season baseflow appears to be more highly connected to the massive natural storage capacity of extensive wetlands in the puna (alpine grasslands) than with cryospheric water inputs. The extent and conservation of puna ecosystems and glacier reservoirs may be interdependent, bringing to bear important conservation questions in the context of changing climate and land use in the region. More generally, this case study demonstrates an efficient combined remote sensing and field observation approach to address data scarcity across regional scales in mountain basins facing imminent rapid change.