The Buriganga River, bordering Dhaka, Bangladesh, is subject to sustained industrial and municipal discharge, resulting in significant water quality degradation. This study presents a seasonally comparative assessment of hydrochemistry, dissolved heavy metals, pollution indices, multivariate relationships, and associated ecological and human-health risks based on sampling at 16 stations during the dry (February 2022) and wet (September–October 2022) seasons. Nutrient concentrations indicated substantial enrichment, with nitrate (NO₃−) reaching up to 2469 mg/L at localized highly impacted stations, likely reflecting point-source sewage and urban wastewater inputs. Dissolved metals, particularly Fe, Mn, Pb, and Ni, showed a clear trend of downstream increase. Multivariate analyses (PCA, FA, HCA) revealed structured associations among metals that are consistent with urban–industrial influence, with seasonal variation likely linked to runoff and sediment remobilization. Non-carcinogenic risk remained below regulatory thresholds (HI < 1), whereas cadmium-associated carcinogenic risk fell within the 10−6–10−4 management range, with localized downstream maxima. Ecological assessment indicated moderate to high cumulative hazard in downstream reaches, particularly during the wet season. The HSPI suggests that downstream risk patterns are driven more by seasonal amplification than by persistent elevation under both hydrological conditions. Overall, the results suggest that sustained anthropogenic inputs influence the spatial contamination pattern, while seasonal hydrology modulates the magnitude of associated risks in the Buriganga River.