For more efficient use of membrane technology in water treatment, it is essential to understand more about the fouling that requires chemical cleaning to be eliminated (i.e., irreversible fouling). In this study, five different MF/UF membranes and four types of organic matter collected from different origins were examined in terms of the degree of irreversible membrane fouling. Experimental results demonstrated that the extent of irreversible fouling differed significantly depending on the properties of both the membrane and organic matter. Among the tested membranes, UF membranes made of polyacrylonitrile (PAN) exhibited the best performance in terms of prevention of irreversible fouling. In contrast, MF membranes, especially one made of polyvinylidenefluoride (PVDF), suffered significant irreversible fouling. Conventional methods for characterization of organic matter such as specific ultraviolet absorption (SUVA), XAD fractionation, and excitation-emission matrix (EEM) were found to be inadequate for prediction of the degree of irreversible fouling. This is because these analytical methods represent an average property of bulk organic matter, while the fouling was actually caused by some specific fractions. It was revealed that hydrophilic fraction of the organic matter was responsible for the irreversible fouling regardless of the type of membranes or organic matter.