In a polymer-flooding wastewater treatment process, physically irreversible fouling of ultrafiltration (UF) membranes is severe and inevitable. Particularly, anionic polyacrylamide (APAM) aggravated flux loss is a challenge in flux recovery. Chemical cleaning procedures for polyvinylidene fluoride (PVDF) UF membranes fouled by polymers (e.g., APAM) were designed by investigating their cleaning efficiency, synergistic effect and molecular interactions based on the molecular mechanisms of polymeric fouling. The cleaning efficiency and foulant–foulant intermolecular interactions indicated that the destruction of the hydrogen-bonded network, egg-box shaped gel network, and interpenetrating polymer network using sodium hypochlorite (NaClO), ethylenediaminetetraacetic acid (EDTA) and dodecyl trimethyl ammonium chloride (DTAC) solutions, respectively, led to significant flux recovery. The synergistic relationships between the two types of cleaning reagents were different in the mixed solutions and sequential procedures. In addition, oil emulsions facilitated the removal of APAM and slowed the flux loss. Finally, the flux recoveries and operational aspects in the pilot-scale UF experiments indicated that integration of the tested chemical cleaning procedures can efficiently remove membrane foulants and significantly restore membrane flux during polymer-flooding wastewater treatment of UF processes. These results are promising for controlling membrane fouling due to polymeric foulants.