This study investigated the ultrafiltration (UF) membrane fouling mechanism of intracellular organic matter (IOM) from Chlorella vulgaris (CV) and Microcystis aeruginosa (MA). Both CV- and MA-IOM caused severe membrane fouling during UF; however, there were significant differences in the membrane fouling by these two materials. Neutral hydrophilic (N-HPI) compounds were the organics that caused the most severe membrane fouling during CV-IOM filtration, whereas the MA-IOM membrane fouling was induced by mainly hydrophobic (HPO) organics. From an analysis based on Derjaguin-Landau-Verwey-Overbeek theory, it was found that the interaction energy between the membrane and foulants in the later stage of filtration was the major factor determining the efficiency of filtration for both CV-IOM and MA-IOM. The TPI organics in CV-IOM fouled the membrane to a more severe degree during the initial filtration flux; however, when the membrane surface was covered with CV-IOM foulants, the N-HPI fraction of CV-IOM caused the most severe membrane fouling because its attractive energy with the membrane was the highest. For MA-IOM, regardless of the initial filtration flux or the late stage of filtration, the HPO organics fouled the membrane to the greatest extent. An analysis of modified filtration models revealed that cake layer formation played a more important role than other fouling mechanisms during the filtration of CV-IOM and MA-IOM. This study provides a significant understanding of the membrane fouling mechanism of IOM and is beneficial for developing some strategies for membrane fouling control when treating MA and CV algae-laden waters.