Freshwater amphipods play a key role as forage for breeding and migrating waterfowl in wetlands throughout the Prairie Pothole Region (PPR) of North America. Amphipod populations declined in recent decades, but there is a limited understanding of mechanisms for their decline and their uneven distribution across the landscape. Row crop agriculture is abundant in the PPR, but the sensitivity of amphipods and wetland ecosystems to agrochemical pollution has rarely been studied. We investigated relationships among amphipod abundances (specifically, Gammarus lacustris and Hyalella azteca), land uses, water quality, and pyrethroid insecticide contamination of wetland sediments. Our study design targeted a large gradient of amphipod abundances and accounted for water quality, hydrology, and habitat metrics that commonly influence amphipods. We found a significant, negative relationship between pyrethroid concentrations and the abundance of the two amphipod species. Pyrethroids were detected at relatively low concentrations (<2.5 ng/g sediment) in 44% of study wetlands and occurred most frequently in intensively cropped watersheds with low vegetative filter strip coverage. Interestingly, wetlands on state and federal wildlife reserves had regular occurrence of pyrethroids, demonstrating the pervasive transport of these compounds and the intensity of agriculture in the PPR. The pyrethroids are likely entering these wetlands through overland transport during rain events or aerial spray drift, and our results show that forest patches and vegetative filter strips may reduce pyrethroid exposure to both wetlands and amphipods.