Snowmelt is a crucial source of water for many shallow subarctic lakes, but climate models predict that snowfall will decrease in some regions, with profound ecological consequences. Here we use lake water isotope data across gradients of terrestrial vegetation cover (open tundra to closed forest) and topographic relief to identify lakes that are vulnerable to desiccation under conditions of low snowmelt runoff in two subarctic landscapes—Old Crow Flats, Yukon, and Hudson Bay Lowlands, Manitoba (Canada). Lakes located in low-relief, open tundra catchments in both landscapes displayed a systematic, positive offset between directly measured lake water δ18O over multiple sampling campaigns and lake water δ18O inferred from cellulose in recently deposited surface sediments. We attribute this offset to a strong evaporative 18O-enrichment response to lower-than-average snowmelt runoff in recent years. Notably, some lakes underwent near-complete desiccation during midsummer 2010 following a winter of very low snowfall. Based on the paleolimnological record of one such lake, the extremely dry conditions in 2010 may be unprecedented in the past ~200 years. Findings fuel concerns that a decrease in snowmelt runoff will lead to widespread desiccation of shallow lakes in these landscapes.