One of the world's crucial areas for crude oil exploration and extraction is the southern Gulf of Mexico, where Terminos Lagoon (TL) is located. Sediments from the TL region were used to assess the spatial patterns, origins, and ecotoxicological risks associated with 16 priority polycyclic aromatic hydrocarbons (PAHs; 3.1–248.9 ng⸳g−1 dry weight basis, dw) and trace metals (Ni = 11.0–104.0 mg⸳kg−1; V = 2.0–35.0 mg⸳kg−1 dw) linked to anthropogenic activities. Although origin indices based on PAHs and metals concentrations indicate no crude oil pollution in the region, sources of pyrogenic PAHs were identified. A chemometric approach demonstrated associations between organic matter and PAHs, and that metal accumulation depends mostly by the input of lithogenic materials. Ecotoxicological risk estimations showed a higher risk of possible adverse effects in sites near swamps and mangrove zones, highlighting the need of future monitoring. This study provides a reference for policymakers to conserve Mexico's largest coastal lagoon and other oil-impacted coastal areas worldwide.