This study investigates the fouling mechanisms in membrane distillation, focusing on the impact of foulant type and membrane surface chemistry. Interaction forces between a surface-functionalized particle probe simulating a range of organic foulants and model surfaces, modified with different surface energy materials, were measured by atomic force microscopy. The measured interaction forces were compared to those calculated based on the experimentally determined surface energy components of the particle probe, model surface, and medium (i.e., water). Surfaces with low interfacial energy exhibited high attractive interaction forces with organic foulants, implying a higher fouling potential. In contrast, hydrophilic surfaces (i.e., surfaces with high interfacial energy) showed the lowest attractive forces with all types of foulants. We further performed fouling experiments with alginate, humic acid, and mineral oil in direct contact membrane distillation using polyvinylidene fluoride membranes modified with various materials to control membrane surface energy. The observed fouling behavior was compared to the interaction force data to better understand the underlying fouling mechanisms. A remarkable correlation was obtained between the evaluated interaction force data and the fouling behavior of the membranes with different surface energy. Membranes with low surface energy were fouled by hydrophobic, low surface tension foulants via "attractive" and subsequent "adsorptive" interaction mechanisms. Furthermore, such membranes have a higher fouling potential than membranes with high or ultralow surface energy.