Sustainable approaches are needed to track status and trends of lake water balances in complex, remote freshwater landscapes. Here we use water isotope composition measured at ~60 lakes and 9 river sites three times during the 2015-2019 ice-free seasons at the internationally recognized Peace-Athabasca Delta (Canada) to characterize temporal and spatial patterns in lake water balances and influential hydrological processes. Calculation of evaporation-to-inflow ratios using a coupled-isotope tracer approach, employment of generalized additive models and geospatial ‘isoscapes’ identified areas vulnerable to mid-summer evaporative lake-level drawdown and areas more resilient due to replenishment by river floodwaters during spring ice-jams and the open-water season. The former largely defines the northern, relic Peace sector whereas the latter typifies the more active floodplain environment of the southern Athabasca sector. Ability to capture the marked temporal and spatial heterogeneity in lake water balances serves as a foundation for ongoing isotope-based hydrological monitoring.