Fouling is one of the main issues hampering the implementation of thermally-driven membrane distillation (MD). While the mutual influence of driving force and fouling deposition has been critically assessed in pressure- and osmotically-driven processes, fouling mechanisms have not been fully understood in MD. Using non-invasive optical coherence tomography, this study describes for the first time the evolution of resistance and driving force evolution during the development of the organic fouling layer in direct contact MD. Foulant layer thickness was found to be strongly and linearly correlated to water flux under different conditions of feed temperature and cross-flow velocity. Experimental and modeling results indicate that this phenomenon is associated to the increase of the overall resistance to water vapor transport. With a clean membrane, heat loss is mainly governed by the permeate flux and by temperature polarization. As fouling evolves over time, temperature polarization and additional fouling resistance increase, impacting negatively the water flux and the heat transfer from feed to permeate. Indeed, foulant accumulation was observed to lead to a gradual reduction of heat transfer from the feed to the permeate side, causing a steady increase of the average nominal driving force, i.e., difference between vapor pressure in the feed bulk and in the permeate bulk. The driving force and the resistance evolved together during this dynamic process of fouling development, resulting in the achievement of a near-stable flux value over time.