Extensive pesticide usage in modern agriculture represents a considerable anthropogenic stressor to freshwater ecosystems throughout the United States. Acute toxicity of three of the most commonly used agricultural pesticides (Methyl Parathion 4ec, Tempo SC Ultra, Karmex DF, and DDT) was determined in two different wild-caught strains of the fairy shrimp Thamnocephalus platyurus. Fairy shrimp collected from playas surrounded by native grasslands were between 200% and 400% more sensitive than fairy shrimp derived from playas in agricultural watersheds for Methyl Parathion 4ec, Tempo SC Ultra, and Karmex DF, likely due to the development of resistance. Additionally, reduced sensitivity to DDT was observed among fairy shrimp from agriculturally-impacted playas as compared to those from native grassland-dominated playas. These data suggest that fairy shrimp inhabiting playas in agricultural regions have developed some degree of resistance to a variety of agrochemicals in response to historical usage.