There have been increasing concerns regarding antimicrobial contaminants in the environment. To date, limited research exists regarding the fate and transport of these compounds in the environment once they have been discharged in human and animal wastes. The fate and transport of two antimicrobials, sulfadimethoxine (SDM) and ormetoprim (OMP), were investigated in two soils and a sand using miscible pulse and step displacement column studies. Because OMP and SDM are often administered in combination, their fate and transport were investigated individually as single solutes as well as in combination as cosolutes. The transport of SDM and OMP was modeled by the chemical nonequilibrium model of the convection–dispersion equation. Sorption of SDM in soils and sand was found to be weak (i.e., it readily desorbed); OMP was sorbed more strongly and required more time for desorption. Results for the pulse input columns yielded mass recoveries >0.90 for the sand and two soils with SDM and for the sand with OMP. Mass recoveries of OMP in the two soils were 0.56 and 0.55, respectively, indicating irreversible sorption or chemical transformation. Comparisons of single-solute and cosolute column studies of OMP and SDM indicate that sorption and transport of these compounds in mixtures were not considerably different from their individual sorption and transport. Overall, the results from this study indicate that both compounds have the potential to move through soils, contaminating nearby surface waters and groundwater.