Sulfonamide antimicrobial agents are widely used in human medicine and animal husbandry. They enter soil environments through effluent irrigation and application of manure and sewage biosolids as soil amendments. The primary concern with introducing antimicrobial agents into soil and water environments is the spread of antibiotic resistance in response to increased selective pressure, potentially leading to proliferation of resistant pathogens. The interaction of sulfonamide antimicrobials with soil constituents influences their mobility and bioavailability. Mineral clay and humic substance are two important components in soil, which are usually associated with each other. In this study, we examined the sorption and desorption of sulfamethazine to three reference smectite montmorillonites (Ca-SWy-2, Ca-SAz-1 and Ca-SWa-1) with humic acid coatings (Elloit Soil humic acid, Summit Hill humic acid) at humic acid to clay ratios of 1:5, 1:50 and 1:100. Batch sorption experiments were conducted in 5 mM CaCl2 for 7 days and the solid to liquid ratio was 5 mg/mL. The desorption of sulfamethazine from humic-clay complexes was investigated using a single decant-refill procedure for 2 days equilibrium, the ratio of sulfamethazine-free solution to total solution was 0.95. Both sorption and desorption isotherms well fit by the Freundlich Model. Sorption of sulfamethazine to humic-clay complexes was non-linear (n < 1, p < 0.05) over the investigated concentration range. Increased humic acid loading enhanced sulfonamide sorption and slightly decreased isotherm linearity. Desorption hysteresis was observed and was higher at lower humic acid loadings. Apparent competitive sorption with another sulfonamide (sulfapyridine) was observed for clays with high humic acid loadings.