This study proposed and applied an innovative heat/powdered activated carbon (PAC)/persulfate (PS) pre-treatment system for the first time in an aerobic granular sludge–membrane system (AGSMS). We examined the effects of the heat/PAC/PS system on membrane fouling mitigation and contaminant removal and qualitatively evaluated the contribution of adsorption and oxidation to membrane fouling control. Compared to other pre-treatment systems, the heat/PAC/PS system could enhance the removal of pollutants, reduce fouling resistance, and delay the decline of permeation flux, resulting in low foulant content on the membrane surface and formation of a loose and porous cake layer. According to radical scavenging experiments, the excellent heat/PAC/PS system pre-treatment performance was attributed to the PAC adsorption capacity and non-radical oxidation pathway. Thermal synergy played a significant role in promoting adsorption and oxidation abilities. The extended Derjaguin–Landau–Verwey–Overbeek theory indicated that the high-energy barrier in the heat/PAC/PS system was an important factor in inhibiting the adhesion of foulants to the membrane surface. Furthermore, the correlation analysis suggested that membrane fouling control should focus on the removal of chemical oxygen demand and suspended solids. This study provides a new approach for membrane fouling mitigation through AGSMS in municipal wastewater treatment.