We investigated the occurrence, origin, and potential ecological risk of dissolved polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyl (PCBs) and organochlorine pesticides (OCPs) in 27 surface water samples collected from a highly anthropized and industrialized area in the Gulf of Gabès (Tunisia, Southern Mediterranean Sea) in October–November 2017. The results demonstrated a wide range of concentrations (ng L−1) with the following decreasing order: Ʃ16 PAHs (17.6–71.2) > Ʃ20 PCBs (2.9–33.7) > Ʃ6 DDTs (1.1–12.1) > Ʃ4 HCHs (1.1–14.8). Selected diagnostic ratios indicated a mixture of both pyrolytic and petrogenic sources of PAHs, with a predominance of petrogenic sources. PCB compositions showed distinct contamination signatures for tetra- to hepta-chlorinated PCBs, characteristic of contamination by commercial (Aroclor) PCB mixtures. The dominant OCP congeners were γ-HCH, 2,4′-DDD and 2,4′-DDE, reflecting past use of Lindane and DDTs in the study area. Agricultural, industrial and domestic activities, as well as atmospheric transport are identified as potential sources of PAHs, PCBs and OCPs in surface waters of the Gulf of Gabès. Toxic equivalents (TEQs) suggested a low carcinogenic potential for PAHs in seawater samples (mean of 0.14 ng TEQ L−1). Evaluation of risk coefficients revealed low risk for PAHs and PCBs, and moderate to severe risk for OCPs.