The Suez Canal suffers from heavy maritime traffic, especially oil tankers, due to its strategic location between the Mediterranean and the Red Sea. As a result, it is prone to accidental oil spills, which might obstruct the maritime lane via the canal and severely harm the marine and coastal ecosystems. This study aims to forecast an oil spill trajectory and fate under the influence of different wind regimes using the General NOAA Operational Modeling Environment (GNOME) and the Automated Data Inquiry for Oil Spills (ADIOS2) models to define the potentially affected regions. Hence, four scenarios were simulated, assuming a spill of one thousand metric tons of Arabian light crude oil into the seawater about two kilometers from the Suez Canal’s southern entrance. The results highlight that wind direction and sea currents substantially affect the movement of oil spills. The trajectory maps show that the north-west wind forces the spilled oil to move toward the southeast direction, threatening the navigation lane through the Suez Canal and about 38 km of beaches south of the canal, which has several vital projects such as the Ayoun Mousse power plant and a lot of resorts. In the case of northern winds, the oil moved south in the center of the Gulf, which may allow response teams more time to clean up the spill. However, in the case of north-east winds, the oil drifted southwesterly and threatened the Green Island and western shores of the Gulf, which has many tourist villages. About a quarter of the oil evaporated, and more than two-thirds of the oil emulsified in all four scenarios. For the first time, this study has provided an understanding of oil spill forecasting and trajectory modeling for the Suez Canal’s southern entrance. Also, it can be considered a prediction tool for Egypt’s policymakers and Suez Canal Authority (SCA) to develop adequate and practical strategies to mitigate crude oil spill consequences.