Synthetic chemicals, such as pesticides, have increased faster than other agents of global change have, yet their ecological impacts remain understudied. Additionally, agricultural expansion to address human population growth and food shortages is predicted to increase the use of pesticides, some of which have been linked to increases in infectious diseases of humans, such as schistosomiasis, which infects >250 million people worldwide. Previous work revealed that ecologically relevant concentrations of organophosphate and pyrethroid insecticides are highly toxic to crayfish. Whether these same insecticides are also highly toxic to Macrobrachium rosenbergii and M. vollenhovenii prawns, which are closely related to crayfish and are important predators on snails that transmit schistosomiasis in Asia and Africa, respectively, is unknown. We performed laboratory dose-response studies for M. rosenbergii using three pyrethroid (esfenvalerate, λ-cyhalothrin, and permethrin) and three organophosphate (chlorpyrifos, malathion, and terbufos) insecticides. Pyrethroid LC50 values were consistently several orders of magnitude lower than for organophosphate insecticides. Pyrethroids also had a greater likelihood of field runoff at levels lethal to prawns. To corroborate these findings in natural settings, we experimentally tracked survival of individually caged M. vollenhovenii at 31 waterways in West Africa that varied widely in their insecticide use. Consistent with laboratory results, pyrethroid insecticide use in these villages was positively associated with Macrobrachium mortality when controlling for village-level and prawn-level attributes, including levels of organophosphate applications. Villages with the most pyrethroid use had lower prawn survival, despite using on average 20% less total insecticides than villages with high prawn survival. Our findings suggest that pyrethroid insecticides widely used in sub-Saharan Africa have strong non-target effects on Macrobrachium spp. prawns, with possible implications for human schistosomiasis. Thus, regulations or incentives to avoid high-risk insecticides, especially near waterways, could have important human health implications in countries undergoing agricultural expansion in schistosomiasis-endemic regions.