This study investigated the fouling of pressure-driven ultrafiltration (UF) membrane and osmotically-driven forward osmosis (FO) membrane by organic macromolecules. Protein and humic acid, two types of ubiquitous identified membrane organic foulants, were chosen as the model foulants. It was found that the hydrodynamic conditions (initial flux and cross-flow velocity) and feedwater composition (foulant concentration, pH, ionic strength, and divalent ions concentration) played a significant role on the organic fouling of these two types of membranes. During the bovine serum albumin (BSA) ultrafiltration, drastic flux reduction was observed at high initial flux and/or low cross-flow velocity. A limiting flux existed during BSA filtration, beyond which membrane flux can not be sustained. Further increase in pressure over the limiting value did not enhance the stable flux. Foulant concentration had no effect on the stable flux, although the rate approaching to the stable flux increased proportionally with increasing foulant concentration. Fouling was most severe at the isoelectric point (IEP) of BSA (pH 4.7), where the electrostatic repulsion between foulant molecules is negligible. Membrane fouling became less severe at pHs away from the IEP. Increasing the ionic strength at pH 3.0 promoted severe fouling likely due to electric double layer (EDL) compression.