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Although pesticide contamination in agricultural surface waters is a common phenomenon, large-scale studies dealing with the responsible drivers are rare. We used data from 259 publications reporting 5830 individual water or sediment concentrations of 32 insecticides and their metabolites in 644 US surface waters to determine the factors driving insecticide risks, that is, exceedance of regulatory threshold levels (RTLs). Multiple linear regressions (R² adj. = 49.6–76.5) revealed that toxicity-normalized agricultural insecticide use (i.e. use divided by toxicity) was the most important driver. Burst rainfall erosivity and irrigation practices also had risk-promoting effects, whereas time, catchment size, and sampling interval had risk-demoting effects. A regression model (R² adj. = 62.2, n = 1833) for small, medium, and large running waters was validated and used for risk mapping at the national scale, highlighting multiple …