Sulfadimethoxine is a widely used sulfonamide veterinary antibiotic and could be a source of agricultural contamination. Therefore, information is needed about its degradation kinetics in manure under aerobic conditions. Based on the analysis of first-order kinetics and the assumption that sulfadimethoxine availability for degradation in manure could be limiting, a new kinetic model was developed and was found to fit the degradation kinetics well. The degradation rate in sterile manure was found to be much lower than in nonsterile manure, indicating that biodegradation was significant. In biologically active manure, the degradation rate constant decreased with increasing initial concentration of sulfadimethoxine, implying that the activity of the degrading microorganisms was inhibited. Increasing moisture or temperature was found to increase sulfadimethoxine degradation in manure. Mixing manure containing high levels of sulfadimethoxine with manure containing lower levels may result in more rapid degradation, thus greatly diminishing sulfadimethoxine contamination in manure and significantly reducing sulfadimethoxine inputs into the environment. During treatment, keeping the manure moist and storing in a moderately warm place under aerobic conditions may also help to diminish sulfadimethoxine contamination.