The herbicide chlorsulfuron is commonly applied to cereals and may persist in alkaline soil long enough to damage subsequent sensitive crops. Sewage water, a potential source of the heavy metal cadmium (Cd), is used to irrigate agricultural soils in many developing countries. The current work evaluated the effects of the residual herbicide chlorsulfuron and Cd on maize seedlings, with particular attention to the mechanism of their action on plant growth. Maize seeds were planted in soil that had been sprayed with chlorsulfuron and Cd, after which residues in both seedlings and the soil were measured. The chlorsulfuron dose was correlated with the amount of residue found in seedlings but not in the soil. In all, 39 metabolites were identified in seedlings using the Automated Mass spectral Deconvolution and Identification System software program and the retention index method. The combination of chlorsulfuron and Cd significantly reduced multiple metabolites in the shikimate pathway, malic acid and citric acid production in the tricarboxylic acid cycle, and lactic acid, glucose, aspartic acid, asparagine and 3-glycerophosphoric acid production. In addition, chlorsulfuron caused an increase in multiple amino acids, including tyrosine, methionine and asparagine, and a marked decrease in caffeic and cinnamic acids (the secondary metabolites derived from the shikimate pathway and galactose). Finally, chlorsulfuron and Cd stress markedly increased shikimate acid, decreased 3-glycerophosphoric acid and caused negative correlations between the amounts of phenylalanine and tyrosine and those of quinic- and cinnamic-acid. In conclusion, chlorsulfuron and Cd did not have a synergistic effect on maize seedlings; rather, the combination of these pollutants had an antagonistic effect on some amino acids.