The adsorption and desorption mechanisms of natural organic matter (NOM) on mineral surfaces are not completely understood because of the heterogeneity and complexity of NOM and adsorbent surfaces. This study was undertaken to elucidate the interaction mechanisms between NOM and iron oxide surfaces and to develop a predictive model for NOM adsorption and desorption. Results indicated that ligand exchange between carboxyl/ hydroxyl functional groups of NOM and iron oxide surfaces was the dominant interaction mechanism, especially under acidic or slightly acidic pH conditions. This conclusion was supported by the measurements of heat of adsorption (microcalorimetry), FTIR and I3C NMR analysis, and competitive adsorption between NOM and some specifically adsorbed anions. A modified Langmuir model was proposed in which a surface excess-dependent affinity parameter was defined to account for a decreasing adsorption affinity with surface coverage due to the heterogeneity of NOM and adsorbent surfaces. With three adjustable parameters, the model is capable of describing a variety of adsorption isotherms. A hysteresis coefficient, h, was used to describe the hysteretic effect of adsorption reactions that, at h = 0, the reaction is completely reversible, whereas at h = 1, the reaction is completely irreversible. Fitted values of h for NOM desorption on iron oxide surfaces ranged from 0.72 to 0.92, suggesting that the adsorbed NOM was very difficult to be desorbed at a given pH and ionic composition. Our results imply that a better mechanistic understanding of the interaction between NOM and oxide surfaces is needed to improve our predictive capabilities in NOM transport and cotransport of contaminants associated with NOM or iron oxides.