Intensified agricultural activities increase wastewater discharge into coastal lagoon systems, with high levels of organic matter, nutrients, and pesticides. This study monitored and assessed environmental conditions at a key agricultural drainage site to assess ecological risk to a Ramsar lagoon system. The Water Pollution Index (WPI) and Risk Quotient (RQ) were applied jointly to identify priority pollutants and their potential impact on the lagoon system of international ecological importance. Sampling was conducted over 4 years in an agricultural drain in northwestern Mexico, where farming, livestock, and poultry effluents converge. Physicochemical parameters, nutrients, and pesticides were determined using standardized methods and gas chromatography coupled with mass spectrometry. The overall WPI value was 1.07, ranking the water as highly polluted. Chemical oxygen demand (1051 mg/L) and total suspended solids (155 mg/L) contributed most to the index, reflecting a high load of recalcitrant organic matter. Eighteen pesticides from different chemical groups were identified, including thiamethoxam, acetamiprid, chlorpyrifos, and diazinon, which had the highest RQ values (≥ 0.8), indicating a significant ecological risk to aquatic organisms. The coexistence of organic pollutants and nutrients suggests cumulative and synergistic effects that compromise the stability of the lagoon system. There is technical evidence of the need to implement strategies for the treatment and sustainable management of agricultural wastewater, promoting its reuse in line with the principles of the circular economy.