Rapidly changing climate is disrupting the High Arctic’s natural water systems. This disruption demands high quality monitoring of Arctic hydrology to better reconstruct past changes, track ongoing transformations, and assess future environmental threats. Water isotopes are valuable tracers of hydrological processes, but logistical challenges limit the length and scope of isotopic monitoring in High Arctic landscapes. Here, we present a comprehensive isotopic survey of 535 water samples taken in 2018–2019 of the lakes, streams, and other surface waters of the periglacial Pituffik Peninsula in far northwest Greenland. The δ¹⁸O, δ²H, and deuterium-excess values of these samples, representing 196 unique sites, grant us unprecedented insight into the environmental drivers of the region’s hydrology and water isotopic variability. We find that the spatial and temporal variability of lake isotopes is dominated by evaporation and connectivity to summer meltwater sources, while evaporation determines interannual isotopic changes. Stream isotopic compositions vary in both space and time based on the relative source balance of tundra snowpack meltwater versus surface melt from the nearby Greenland Ice Sheet. Overall, our survey highlights the diversity of isotopic composition and evolution in Pituffik surface waters, and our complete isotopic and geospatial database provides a strong foundation for future researchers to study hydrological changes at Pituffik and across the Arctic. Water isotope samples taken at individual times or sites in similar periglacial landscapes likely have limited regional representativeness, and increasing the spatiotemporal extent of isotopic sampling is critical to producing accurate and informative High Arctic paleoclimate reconstructions.