We present new mathematical and geological models to assist civil protection authorities in the mitigation of potential oil spill accidents in the Eastern Mediterranean Sea. Oil spill simulations for 19 existing offshore wells were carried out based on novel and high resolution bathymetric, meteorological, oceanographic, and geomorphological data. The simulations show a trend for east and northeast movement of oil spills into the Levantine Basin, affecting the coastal areas of Israel, Lebanon and Syria. Oil slicks will reach the coast in 1 to 20 days, driven by the action of the winds, currents and waves. By applying a qualitative analysis, seabed morphology is for the first time related to the direction of the oil slick expansion, as it is able to alter the movement of sea currents. Specifically, the direction of the major axis of the oil spills, in most of the cases examined, is oriented according to the prevailing azimuth of bathymetric features. This work suggests that oil spills in the Eastern Mediterranean Sea should be mitigated in the very few hours after their onset, and before wind and currents disperse them. We explain that protocols should be prioritized between neighboring countries to mitigate any oil spills.