Four hundred tons of sulfamethazine are fed to livestock annually in North America to prevent disease and promote growth, but most of the drug is excreted unmetabolized into the environment. Because of slow degradation and high mobility, sulfamethazine contaminates groundwater supplies and causes aquatic ecosystem damage. Current water treatment methods to remove pharmaceuticals are not universally effective and have considerable limitations, which necessitate newer remediation techniques. Hypercrosslinked adsorbents, polystyrene polymers 100% crosslinked with methylene bridges, show promise because of high surface areas, high mechanical strength, and regenerable properties. This study screened four Purolite hypercrosslinked adsorbents (MN152, MN250, PAD400, and PAD600) to remove sulfamethazine from contaminated water and then characterized the most efficient resin, MN250, with batch adsorption and desorption experiments to optimize its use. Sulfamethazine adsorption onto MN250 displayed an L-class isotherm shape consistent with monolayer adsorption, negligible solute-solute interactions at the adsorbent surface, and decreasing activation energies of desorption with increasing surface coverage. MN250 had a maximum experimental adsorption capacity of 111 mg g, showing high correlation to the Langmuir and Freundlich models. Adsorption kinetics revealed prolonged adsorption over 59 h and were best described by Ho's pseudo-second-order model. There was minimal desorption from MN250 in distilled water, indicating an irreversible adsorption process. MN250's high capacity for sulfamethazine adsorption, minimal desorption in water, and ability to be regenerated make it a practical solution for sulfamethazine removal in areas that have contaminated groundwater supplies (e.g., areas near concentrated livestock operations), especially as current treatment methods have significant drawbacks.