In this study, we investigate the influence of surface structure on the fouling propensity of thin-film composite (TFC) forward osmosis (FO) membranes. Specifically, we compare membranes fabricated through identical procedures except for the use of different solvents (dimethylformamide, DMF and N-methyl-2-pyrrolidinone, NMP) during phase separation. FO fouling experiments were carried out with a feed solution containing a model organic foulant. The TFC membranes fabricated using NMP (NMP-TFC) had significantly less flux decline (7.47 ± 0.15%) when compared to the membranes fabricated using DMF (DMF-TFC, 12.70 ± 2.62% flux decline). Water flux was also more easily recovered through physical cleaning for the NMP-TFC membrane. To determine the fundamental cause of these differences in fouling propensity, the active and support layers of the membranes were extensively characterized for physical and chemical characteristics relevant to fouling behavior. Polyamide surface roughness was found to dominate all other investigated factors in determining the fouling propensities of our membranes relative to each other. The high roughness polyamide surface of the DMF-TFC membrane was also rich in larger leaf-like structures, whereas the lower roughness NMP-TFC membrane polyamide layer contained more nodular and smaller features. The support layers of the two membrane types were also characterized for their morphological properties, and the relation between support layer surface structure and polyamide active layer formation was discussed. Taken together, our findings indicate that support layer structure has a significant impact on the fouling propensity of the active layer, and this impact should be considered in the design of support layer structures for TFC membranes.