From the microscopic scale to the petroleum-reservoir scale, the interfacial phenomena of a crude oil–water-rock system crucially control immiscible flow in a porous reservoir. One of the key mechanisms is crude oil droplet displacement dynamics, which can be optimized by manipulating the oil–water interfacial tension and the three-phase contact angle by means of chemical injection. Oil film displacement was enhanced by adding interfacially active nanoparticles, namely poly(N-isopropylacrylamide) or pNIPAM (43–48 nm hydrodynamic diameter and 0.0005–0.0050 wt% concentration range), accelerating the oil droplet receding rate (up to 5.66°/s) and greater degree of oil film dewetting (37.0° contact angle). Such behavior was attributed to nanoparticle-induced structural disjoining pressure between the oil–water and water–solid interfaces. The coupling effect of pNIPAM nanoparticles with low-salinity brines was studied, revealing discrepancy in different valency brines. Coupling with divalent CaCl2 led to much slower oil droplet receding dynamics (2.58°/s, and 58.7° contact angle) since oil-substrate bridging is formulated and promoted by the divalent cation. However, a positive synergy was observed with a monovalent NaCl blend. The crude oil dewetting dynamics were enhanced (9.55°/s) owing to the combined salt-induced hydration and nanoparticle-induced structural forces. The contact angle reduced to 21.5° before eventually detaching from the substrate after a relatively short period (156 s). These findings highlight the coupling effects of nanoparticles and low-salinity brine to enhance dewetting of heavy crude oil. Adding nanoparticles to an ‘optimal’ brine could be an option for faster and greater fluid displacement, which is not limited to oil production applications but several others, such as detergency and other forms of geological storage.