Coastal areas are frequently impacted by anthropogenic pollution, due to intense human activity in these zones. Our study aimed to monitor the impacts of anthropogenic pollution in four Portuguese locations on the northwest coast, and to identify the most affected areas and/or seasons by applying a multi-biomarker approach. Water and specimens of Phorcus lineatus were collected on the rocky shore during low tide in four sites along the northwest Portuguese coast (1. Amorosa; 2. Cabo do Mundo; 3. Homem do Leme; 4. S. Félix da Marinha) with different anthropogenic pressures, including an industrial maritime shipyard; an oil refinery; an international airport; and an area with high human population density. The collection took place over two seasons: the summer of 2021 and the winter of 2022. Several biochemical biomarkers, including reactive oxygen species; protein carbonyl content; lipid peroxidation (LPO); carboxylesterase (CE); and antioxidant (superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), and neurotoxicity—acetylcholinesterase (AChE)) enzymes were measured. The results showed seasonal variation, with the ROS, LPO, CE, and GST activities depending particularly on the season, but the SOD and CAT activities being similar between summer and winter. CAT showed lower activity in Site 1 than in the other sites during both seasons (p < 0.05). The Integrated Biomarker Response (IBR) index showed that biomarker responses were higher in winter. The multivariate analysis confirmed the higher contribution of the factor season to the P. lineatus’ response to pollutants, compared to the spatial variation in the northwest Portuguese coast. Overall, this study shows that P. lineatus can be a suitable bioindicator species for environmental biomonitoring, and that the IBR index allows the identification of temporal contamination patterns.