Lotic ecosystems harbor a disproportionate amount of global biodiversity, but continue to experience extinction rates greater than terrestrial. Alpine rivers and streams are especially threatened due to high rates of warming, glacier melt impacts, landcover change, and impoundment. Lack of monitoring, however, hampers conservation efforts in many regions. The Hindu-Kush Himalaya (HKH) is experiencing rapid environmental change, but impacts on aquatic biodiversity are unknown. Using a unique long-term dataset, we investigated changes to local (alpha) and regional (gamma) fish species diversity across 38 sites on Nepal’s Kaligandaki-Narayani River (KNR), and evaluated potential impacts of climate change. Our results indicate a significant decrease in mean abundance and local species richness, although regional diversity did not decline. Species ranges contracted between the 1990s and 2010s, with lower bounds and weighted means shifting to higher elevations. Range shifts coincided with water temperature warming between the 1990s and 2010s, particularly at more speciose lower elevation sites. Although widespread species loss has not yet occurred, decreasing abundance and contraction of species’ ranges point to increased extirpation risk in the near future. Our results suggest that effective conservation strategies must identify and preserve thermal refugia, maintain habitat connectivity, manage terrestrial protected areas so that aquatic biodiversity also benefits, and establish sustainable fishery harvests to protect species diversity in the KNR and other threatened, under-studied alpine biodiversity hotspots.