The use of a membrane with a relatively loose ‘active layer’ opened a new paradigm for the application of osmotically driven processes. An effective way of imparting the osmotic pressure difference across the ‘active layer’ is to employ divalent salts as the draw solute, whose negative effects on the organic fouling have been documented in the literature. This study was targeted on investigating the fouling by clay suspensions when performing the forward osmosis (FO) with a nanofiltration (NF)-like membrane. Optical coherence tomography (OCT) was exploited to analyze the fouling phenomena in a way of determining the critical point of the initial flux, below which the fouling could be completely or partially inhibited. In comparison with the flux-decline measurements, the OCT-based characterization generated a series of digitalized cake layers for numerically evaluating the surface coverage and specific deposit, which provides direct evidence to support the hypothesis that the back diffusion of the draw solute could have significant impact on the initial deposition of the clay particles. That is, the presence of the draw solute in the boundary layer could favor the slow growth of the cake layer even if the initial flux was lower than the critical point. Mapping the local growth rates also indicates that the increase in affinity between the membrane and the clay particles could vary the characteristics of the instability-induced streamwise vortices. In particular, the markedly decreased critical point of the initial flux highlights the role of divalent cations in forming coordinate bonds between the clay particles and the NF-like membrane. All the characterization results offer valuable knowledge to enhance the design of the novel osmotically driven processes.