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Despite global conservation efforts, freshwater biodiversity declines have continued into the 21st century. Management efforts in many areas are hampered by a lack of data in under-studied areas that harbor high fish species diversity, are under the greatest threat, and have human populations heavily reliant on the services provided by aquatic ecosystems. One such region is the Hindu-Kush Himalaya. Combining a unique long-term dataset with contemporary fieldwork, we investigated changes to fish species diversity and abundance in Nepal’s Kaligandaki-Narayani River, using a modeling approach to evaluate climate change impacts. Our results indicate declines in mean abundance and species richness of fishes per site. During a period of rapid water temperature warming, species ranges contracted, with lower bounds and weighted mean elevations shifting to higher elevations. Given the spatial pattern of species declines, we discuss the potential for effective management strategies that incorporate thermal refugia and terrestrial protected areas.