Oil spills are major threat to marine ecosystem and have long-lasting effect on marine life and water quality. In this study, a two-dimension hydrodynamic and oil spill transport model of the Yangtze River Estuary is established based on MIKE21 with a special attention to wind-wave-current interaction (WWCI). The model agrees well with the observed data on water level, current velocity, and the real oil spill event during Typhoon Fongwong. This study is mainly focused on the oil particle trajectory and spread. The model results show: (1) when the oil spill occurs during a typhoon period, the oil film can rapidly deposit under high WWCI, decreasing the swept area to about 20% compared with the normal weather condition; (2) strong current and large wave enlarge the oil film coverage whereas high wind speeds cause the oil particles to deposit in the shallow water area; and (3) the oil particles move farther and the swept area is far greater under the winter wind than under the summer wind, and the two times of the winter wind show the greatest effect on the oil spill. This study considers the drift, dispersion, evaporation, and emulsification of oil during the moving period under different wind, wave and current conditions, providing a good guidance for the oil spill prevention and mitigation in other estuaries.