Human activities are driving the Earth's sixth mass extinction, and freshwater fish biodiversity has declined sharply over the past century, with approximately one-quarter of freshwater fish species now threatened with extinction. Anthropogenic pressures are expected to intensify due to climate change and continued population growth. Understanding the spatial patterns of freshwater fish imperilment is essential for developing effective conservation policy and prioritising effort. However, such patterns of imperilment have not previously been examined at a global scale. Using IUCN Red List distribution and threat data for 12,954 freshwater fish species, we quantified global imperilment across 190,675 HydroBASINS Level 8 catchments and examined geographic patterns of extinction risk, associated threats, and overlap with protected areas. We found that Europe has the highest proportion of threatened freshwater fish species of any continent, followed by Asia and North America. In contrast, spatial clustering of high-imperilment areas occurs in North Africa, the Middle East, the western United States, Mexico, and Chile, yet existing protected areas provide limited coverage of these regions. Endemic species, as well as species inhabiting freshwater springs and oases, exhibit substantially higher levels of imperilment than other groups. Across all continents, dams and water management are the dominant threats. Agricultural and forestry effluents represent the second-most important threat on every continent except Australia, where invasive species rank second instead. Our findings reveal pronounced geographic variation in the imperilment of freshwater fish and suggest that the current global protected area network provides insufficient coverage to safeguard many of the world's most threatened freshwater fish assemblages.