AbstractFreshwater environments vary widely in ion availability, owing to both natural and anthropogenic drivers. Field and laboratory work point to the importance of overall salinity, as well as cation depletion, in shaping the physiology, behavior, and ecology of freshwater taxa. Yet, we currently have a poor understanding of the degree to which populations may vary in response to ion availability. UsingDaphniacollected from three lakes that differ greatly in salinity and calcium availability, we conducted a laboratory reciprocal transplant experiment to assess how animals representing these populations vary in fecundity, body size, and survival when reared in lake water from each environment. The lake water environment and population of origin strongly interacted to shapeDaphniagrowth and reproduction. Surprisingly, we found only modest evidence that lake water with abundant calcium (5.5 vs. 1.2–2.3 mg/L) increasedDaphniagrowth or reproduction. By contrast, water from a relatively ion‐rich lake (400 μS/cm specific conductance) strongly boostedDaphniafecundity over lower‐ion lake water (20–50 μS/cm), especially for the population originating from the high‐ion environment. Our results suggest that ion‐poor conditions common in regions around the world may exert stress on freshwater organisms, even for populations inhabiting these environments. Meanwhile, moderate salt enrichment may not prove harmful but could even benefit freshwater taxa in these ion‐poor regions. The context dependence of how and when lake water chemistry affectsDaphniaand other freshwater taxa deserves greater attention, in both ion‐depleted and ion‐rich conditions.Daphniaare key members of lake food webs and serve as an important model for ecology, evolution, and toxicology research. Consideration of how lake water chemistry may influence howDaphniapopulations respond to abiotic and biotic stress may improve the ability to evaluate and predict ecological and evolutionary dynamics in lakes of varying chemical composition.