River water pollution and water-related health problems are common issues across the world. The present study aims to examine the Jalangi River’s water quality to assess its suitability for drinking purposes and associated human health risks. The 34 water samples were collected from the source to the mouth of Jalangi River in 2022 to depict the spatial dynamics while another 119 water samples (2012–2022) were collected from a secondary source to portray the seasonal dynamics. Results indicate better water quality in the lower reach of the river in the monsoon and post-monsoon seasons. Principal component analysis reveals that K⁺, NO₃⁻, and total alkalinity (TA) play a dominant role in controlling the water quality of the study region, while, CaCO₃, Ca²⁺, and EC in the pre-monsoon, EC, TDS, Na⁺, and TA in the monsoon, and EC, TDS and TA in the post-monsoon controlled the water quality. The results of ANOVA reveal that BOD, Ca²⁺, and CaCO₃ concentrations in water have significant spatial dynamics, whereas pH, BOD, DO, Cl⁻, SO₄²⁻, Na⁺, Mg²⁺, Ca²⁺, CaCO₃, TDS, TA, and EC have seasonal dynamics (p < 0.05). The water quality index depicts that the Jalangi River’s water quality ranged from 6.23 to 140.83, i.e., excellent to unsuitable for drinking purposes. Human health risk analysis shows that 32.35% of water samples have non-carcinogenic health risks for all three groups of people, i.e., adults, children, and infants while only 5.88% of water samples have carcinogenic health risks for adults and children. The gradual decay of the Jalangi River coupled with the disposal of urban and agricultural effluents induces river pollution that calls for substantial attention from the various stakeholders to restore the water quality.