AbstractChanges in the thermal structure of lake ecosystems have been documented as a response to climate change, but the dynamics of biomass distribution, which fundamentally determines species conservation, has been less studied. An interdisciplinary approach was used to demonstrate the influence of climate‐driven changes on the environmental DNA (eDNA) distribution of two species (Gymnogobius isaza and Palaemon paucidens) in Lake Biwa, the largest monomictic lake in Japan. In field surveys in 2016–2017 (full water circulation) and 2019 (partial water circulation), eDNA concentrations of these species were measured for 43 and 47 samples, respectively, collected from the lake bottom. The correlative relationship was investigated between species' eDNA concentrations and environmental variables. The species–environment relationship was then applied to species' eDNA distributions under existing and future environments calculated by a lake ecosystem model. Based on differences in the estimated eDNA distributions, we suggest that different species respond differently to climate change. The distribution of G. isaza will expand in the future if full water circulation occurs, although it appears to be independent of water circulation at present. Partial water circulation enlarges the distribution area of P. paucidens, but its eDNA concentrations will be low in the future, regardless of the extent of water circulation. These results indicate that species such as P. paucidens, which is now abundant but vulnerable to climate change, require special attention. Furthermore, our study emphasizes the potential application of interdisciplinary methodologies for improved species conservation.