Tylosin(TYL) and sulfamethazine(SMT) are ionizable and polar antimicrobial compounds,which have seeped into the environment in substantial amounts via fertilizing land with manure or sewage. Sorption of TYL and SMT onto humic acid(HA) may affect their environmental fate. In this study, the sorption of TYL and SMT on HA at different conditions(pH, ionic strength) was investigated. All sorption isotherms fitted well to the Henry and Freundlich models and they were highly nonlinear with values of n between 0.5 and 0.8, which suggested that the HA had high heterogeneity. The sorption of TYL and SMT on HA decreased with increasing p H(2.0–7.5), implying that the primary sorption mechanism could be due to cation exchange interactions between TYL~+/SMT~+ species and the functional groups of HA.Increasing ionic strength resulted in a considerable reduction in the K_d values of TYL and SMT,hinting that interactions between H bonds and π–π EDA might be an important factor in the sorption of TYL and SMT on HA. Results of Fourier transform infrared(FT-IR) and ~13C-nuclear magnetic resonance(NMR) analysis further demonstrated that carboxyl groups and O-alkyl structures in the HA could interact with TYL and SMT via ionic interactions and H bonds,respectively. Overall, this work gives new insights into the mechanisms of sorption of TYL and SMT on HA and hence aids us in assessing the environmental risk of TYL and SMT under diverse conditions.