Increasing the cross-flow velocity can improve the permeate flux to a certain extent during cross-flow ultrafiltration harvesting of microalgae. In this study, the effect of cross-flow velocity on the fouling mechanisms of Isochrysis zhanjiangensis suspension, fragile algogenic organic matter-free cells and cell-free algogenic organic matter was investigated using different cross-flow velocities of 0.13, 0.26, 0.51 and 0.63 m.s(-1). The fouling mechanism of algogenic organic matter and algae cells was analyzed by Hermia's model; in particular, the changes in their fouling ratios under different cross-flow velocities were further elucidated based on the criteria importance through intercriteria correlation. The results revealed that cake formation by algogenic organic matter and cells mainly induced membrane fouling at different cross-flow velocities. Notably, the contribution of algogenic organic matter and algae cells to membrane fouling varied with cross-flow velocity. The objective weight of fouling caused by algae cells decreased from 0.758 to 0.279, then increased to 0.560 after cell disruption and finally reached 0.946. This result suggested that the cell disruption significantly aggravated cellular fouling. In contrast, the objective weight of fouling caused by algogenic organic matter increased with cross-flow velocity, and cell disruption reversed the trend. For further insight, a model was developed based on the fouling contributions of algogenic organic matter and cells to cake formation; the model was capable of predicting fluxes under different cross-flow velocities. These findings not only clarify the fouling mechanism of I. zhanjiangensis cells and algogenic organic matter but also provide a valuable model that is instructive for the development of membrane filtration of fragile microorganisms.