Lead (Pb) is a hazardous heavy metal present in the environment which elicits oxidative stress in plants. To characterize the physiological and biochemical basis of Pb tolerance, Prosopis farcta seedlings were exposed to Hoagland's solutions at six different Pb concentrations (0, 80, 160, 320, 400 and 480 μM) for different periods of time. As expected, application of Pb significantly increased hydrogen peroxide (H2O2) content. In response, P. farcta deployed the antioxidative defence mechanisms with significantly higher activities of superoxide dismutase (SOD), enzymes related to H2O2 removal, and also the increases in proline as a solute marker of stress. Increases were observed in nitric oxide (NO) production which could also act in triggering defense functions to detoxify Pb. Enhanced phenylalanine ammonia-lyase (PAL) activity at early days of exposure to Pb was correlated with increases in phenolic compounds. Significant increases in phenolic acids and flavonoids; daidzein, vitexin, ferulic acid and salicylic acid were observed with Pb treatment. Furthermore, the stress effects were followed by changes in free amino acid content and composition. Aspartic acid and glycine content was increased but glutamic acid significantly decreased. It is likely that stress signal transduction by NO and H2O2 mediated defence responses to Pb by coordination of antioxidative system and metabolic pathways of phenylpropanoid and amino acids.