The prairie pothole region (PPR) is among the most extensively altered ecosystems on Earth. This region covers approximately 780,000 km2 of central North America, and contains numerous glacially formed wetlands embedded in an agricultural landscape. These wetlands, commonly known as prairie pothole lakes (PPLs), provide essential ecosystem services. Over the last 150 years, agricultural drainage has resulted in severe loss of native prairie wetlands. The remaining PPLs continue to be threatened by nonpoint source pesticide pollution from agriculture. Currently, little is known about the fate and persistence of pesticides in PPLs. In this work, the abiotic transformations of commonly used pesticides in PPL sediment porewaters and surface water were explored. Chloroacetanilide and dinitroaniline pesticides were found to react rapidly with naturally abundant reduced sulfur species (i.e., hydrogen sulfide and polysulfides) in sediment porewaters via nucleophilic substitution and reduction reactions, respectively. Dissolved organic matter (DOM) was also found to play a vital role in the reductive transformation. Next, the photodegradation of a suite of pesticides was investigated in PPL surface water under both simulated and natural sunlight. Enhanced pesticide removal rates pointed to the importance of indirect photolysis pathways involving photochemically produced reactive intermediates such as singlet oxygen and triplet excited-state DOM. Finally, the sedimentary sulfur speciation was examined by sulfur K-edge X-ray absorption near-edge structure (XANES) spectroscopy. Sulfur species in PPL sediments were found to consist of organic (di)sulfides, sulfonate, sulfate, and the mineral pyrite. Notably, the fractional abundances of reduced and oxidized sulfur species fluctuate on a seasonal basis.