Arsenic and mercury are among the most toxic elemental pollutants in the environment, endangering human health and ecological integrity. Both elements are found in highly thiol‐reactive forms, arsenite and Hg(II), respectively, in plant tissues. Overexpression of Escherichia coliγ‐glutamylcysteine synthetase (ECS) or glutathione synthetase (GS) in Arabidopsis thaliana plants provided significant increases in the thiol peptides glutathione (GSH) and γ‐glutamylcysteine (γ‐EC), and/or phytochelatins (PCs), and some resistance to arsenic and mercury, but no substantial increases in the levels of these elements in above‐ground tissues. In contrast, the co‐expression of ECS and GS in ECS × GS lines produced significant increases in tolerance to toxic levels of mercury. The ECS × GS co‐expression line accumulated 35‐fold more biomass and three‐fold more mercury aboveground than the wild type (WT) when grown on Hg(II). No increases in arsenic accumulation were detected in the ECS × GS line. Increased resistance to and accumulation of mercury apparently resulted from enhanced root concentrations of PCs in ECS × GS co‐expression lines not seen in the wild type or lines expressing ECS or GS alone. Correlations between the levels of arsenic and mercury resistance and accumulation and increases in the accumulation of the various thiol peptides in the ECS, GS and ECS × GS transgenic plant lines are discussed.