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.