This paper evaluates for the first time the spatial distribution of a wide group of organic (phthalates, nitro, aliphatic, halogen, aromatic, phenol and amino compounds) and inorganic pollutants along the Liffey river in Dublin city. The work takes into account the effect of short-term weather conditions on the occurrence of these contaminants. The results showed that rainfall conditions affect the levels of pollutants along the river in the days following a rainfall event. In addition, the tributaries entering the river Liffey were not found to impact its water quality. In relation to organic pollutants, 2,4,6-trichlorophenol, 2-nitrophenol and phthalate compounds were found in many water samples between concentrations of 0.21 and 2.17 μgL−1. On the other hand, dimethyl phthalate was present in certain samples at levels around 100 μgL−1. The levels of these contaminants in the river were lower than the toxicity values reported in the literature. Regarding inorganic pollutants, nitrates were detected from 0.59 to 6.81 mg L−1 increasing from upstream to downstream. Based on the chemical nature and applications of detected pollutants, the river contamination can be mainly related to agricultural, industrial activities as well as diffuse urban contributions. These vary with location within a short distance and have the potential to impact aquatic biodiversity as the chemical composition changes with rainfall events.