This study focused on the mechanistic effects of molecular interactions between inorganic particles (kaolinite) and the two main NOM fouling fractions of polysaccharides (alginate) and humics (humic acids) in ultrafiltration. Fouling effects were studied during the dead-end filtration of individual and mixed compounds as well as during the subsequent filtration of individual compounds. SEM analyses were performed to further study the fouling-layer structure. A significant synergistic effect was observed during combined particle-NOM fouling, which was considerably greater than the sum of particle and organic fouling alone. Synergistic fouling could be explained by NOM-particle interactions in the feed solution and during the fouling process. Kaolinite alone formed a fouling layer of particle aggregates, whereas humic acid adsorption onto kaolinite resulted in a fouling layer of stabilized colloids of humic acid and kaolinite. In the case of alginate, simultaneous pore-blocking and cake-layer formation of NOM and kaolinite dominated the fouling. In both cases, incorporation of the organics in the kaolinite fouling layer resulted in a fouling cake of significantly reduced porosity compared to individual particle filtration. Irreversible fouling by NOM could not be prevented by kaolinite. SEM images showed patches of the particle-fouling layer remaining on the membrane surface after backwashing, which can be linked to particle-membrane associations by NOM bridging.