Nearly one-third of extant freshwater fish species, which account for over 50% of global fish diversity, are at risk of extinction. Despite their crucial ecological and socioeconomic importance, the extinction of freshwater fishes remains under-researched on a global scale. This is a comprehensive assessment of taxonomic, spatial, and temporal patterns of freshwater fish extinctions while identifying key extinction drivers and driver synergies. Using data from the International Union for Conservation of Nature Red List, 89 extinct freshwater fish and 11 extinct in the wild were analyzed. Taxonomic statistical analysis revealed the disproportionate impact on Cyprinidae, Leuciscidae, and Salmonidae. Estimated globally for the period 1851-2016, the modern extinction rate for freshwater fishes stands at 33.47 extinctions per million species-years (E/MSY), more than 100 times greater than the natural background extinction rate of 0.33 E/MSY. Extinction rates, when calculated per continent using the number of extinct species and the total number of species per continent, indicated that North America has the highest extinction rate (225.60 E/MSY), followed by Europe (220.26 E/MSY) and Asia (34.62 E/MSY). Although Africa is less affected, it still shows a 42-fold increase over the background rate. Bayesian modeling, reflecting cumulative species extinctions, indicated a strong association of North America and Asia with species loss (37 and 34 extinctions, respectively), a moderate one for Europe (20 extinctions) and a weak association of Africa (eight extinctions). Natural system modification, pollution, and invasive species emerged as the primary extinction drivers, often acting synergistically. Temporal trends indicate an acceleration in extinctions since the mid-20th century. This study highlights that, despite recent increases in conservation efforts, freshwater fish extinctions continue to rise, indicating the urgent need for integrated conservation strategies. Without immediate action, many species currently at risk may soon follow the same trajectory of extinction as the 100 extinct freshwater fishes of this study.