Pesticides occur in urban streams globally. In studies of five regions of the United States, the U.S. Geological Survey investigated the effects of region and urbanization on the occurrence and potential invertebrate toxicity of dissolved pesticide mixtures, with an emphasis on fungicides and insecticides due to the documented low invertebrate toxicity of herbicides. Models that used summary metrics (EPT and MMI) and those using full species matrix showed tremendous commonality in the pesticides that best explained the response variables. For example, in the Southeast region, the insecticide fipronil was the top variable identified in all three model types (boosted regression tree (BRT), generalized additive model (GAM), distance-based linear model (DISTLM), while in the Pacific Northwest two fungicides and chlordane were important in BRT and DISTLM models, whereas three insecticides (imidacloprid, bifenthrin, and chlordane) were significant variables in the GAM. These same three insecticides were also important variables in the Northeast GAM and the first two insecticides in the California GAM. Pyrethroid insecticides were most important in the Midwest, the only region dominated by agricultural land use. The response forms of the invertebrate MMI for both the BRT and GAM models show general sharp declines as the various insecticide and fungicide concentrations increased across the five regions. Pesticide variables consistently appear as important explanatory variables in the models even when other various stressors (sediment/habitat, nutrients, flow, and basic water quality) are incorporated into the models.