Molecular deposition (MD) filming flooding has proved to be an effective enhanced oil recovery (EOR) method in reservoirs where recovery was relatively difficult. The B425 block with a low permeability in Shengli Oilfield, China, has reaped the benefits of MD filming flooding. However, the main EOR mechanisms and the influencing factors in this block are still not clear. In this work, laboratory experiments were conducted under various conditions to investigate the EOR mechanisms of MD filming flooding and its potential use in enhancing the recovery of low-permeability reservoirs. Spontaneous imbibition, micromodel displacement, and oil–water relative permeability experiments were also performed. The results indicate that a MD filming flooding agent (MDFFA) with lower molecular weight can more effectively reduce the interfacial tension (IFT) and perform better in wettability alteration. The improvement of seepage capacity is obviously increased when the molecular weight of the MDFFA is less than 1000 g/mol. The low molecular weight MDFFA has a better effect on the spontaneous imbibition in a capillary with a larger diameter, and increasing the concentration can enhance this process. Lower injection rate and lower injection concentration are beneficial to reduce the injection pressure and improve oil recovery. The smaller the permeability of cores, the greater the relative permeability difference between water flooding and MD filming flooding. In addition, lower core permeability is more conductive to the EOR mechanisms of MD filming flooding in the low-permeability oil reservoirs.