Coastal seas are important pools of persistent organic pollutants (POPs) discharged from land. Considering the complex conditions in coastal seas and various biochemical features of POPs, special temporal-spatial variations in POPs have been reported. To understand these variations, we developed a three-dimensional hydrodynamic–ecosystem–POP coupled model and applied it to the Yellow Sea. We selected two POP species (polychlorinated biphenyl congener 153 (PCB-153) and decabromodiphenyl ether (BDE-209)), which have different biochemical properties, as target materials. The dissolved PCB-153 simulated concentration was high in late spring and low in autumn, whereas that of BDE-209 was high in summer and low in winter. Both PCB-153 and BDE-209 showed high particle-bound concentrations in early spring. In summer, dissolved PCB-153 accumulated at the sea bottom, whereas dissolved BDE-209 accumulated at the sea surface. Seasonal and spatial variation differences in the two POPs are likely caused by greater Henry’s Law Constant (H′) and bioconcentration factor (BCF) of PCB-153 than that of BDE-209, which leads to higher volatilization and stronger absorption by the particles for PCB-153 than BDE-209. As a component of such differences, the “biological pump” of PCB-153 in the central Yellow Sea is more apparent than that of BDE-209.