In this study, forward osmosis (FO) membranes and fouling solutions were systematically characterized to elucidate the effects of organic fouling on the rejection of two pharmaceutically active compounds, namely, sulfamethoxazole and carbamazepine. Municipal wastewater resulted in a more severe flux decline compared to humic acid and sodium alginate fouling solutions. This result is consistent with the molecular weight distribution of these foulant solutions. Liquid chromatography with organic carbon detection analysis shows that municipal wastewater consists of mostly low molecular weight acids and neutrals, which produce a more compact cake layer on the membrane surface. By contrast, humic acid and sodium alginate consist of large molecular weight humic substances and biopolymers, respectively. The results also show that membrane fouling can significantly alter the membrane surface charge and hydrophobicity as well as the reverse salt flux. In particular, the reverse salt flux of a fouled membrane was significantly higher than that under clean conditions. Although the rejection of sulfamethoxazole and carbamazepine by FO membrane was high, a discernible impact of fouling on their rejection could still be observed. The results show that size exclusion is a major rejection mechanism of both sulfamethoxazole and carbamazepine. However, they respond to membrane fouling differently. Membrane fouling results in an increase in sulfamethoxazole rejection while carbamazepine rejection decreases due to membrane fouling.