The membrane electrochemical reactor (MER), integrating oxidation, softening, and acidification within a single system, has demonstrated significant potential in mitigating membrane fouling during leachate treatment. However, the specific contributions of oxidation, softening, and acidification in the MER, along with their synergistic effects on membrane fouling control, remain inadequately understood. In this study, leachate was regulated with different MER-related strategies before membrane distillation treatment, and Differential logtransformed absorbance spectra, electrochemical impedance spectroscopy, Derjaguin-Landau-VerweyOverbeek theory were employed to investigate the membrane fouling mechanism. The results indicates that oxidation effectively removed the organic matter, thereby mitigating the hydrophobic interactions between the membrane and foulant. However, it also promoted the deprotonation of carboxyl groups in organic matter, such as polysaccharides and proteins, enhancing the complexation of multivalent cations. Acidification and softening reduced organic-inorganic complexation fouling by inhibiting carboxylate deprotonation and reducing Ca2+ and Mg2+ concentrations, respectively. These processes counteracted the adverse effects of oxidation while further mitigating organic fouling and inorganic scaling. Additionally, the synergistic effects of oxidation, softening, and acidification effectively prevented foulants from entering membrane pores and enhanced wetting resistance. Overall, this study demonstrated the potential of combining oxidation, softening, and acidification while elucidating their mechanisms in mitigating membrane fouling.