Background: Lead (Pb) heavy metal pollution in water bodies is one of the serious problems across the world. This study was designed to find out the effect of Pb toxicity on physiological and biochemical changes in Eichhornia crassipes (water hyacinth) seedlings. Results: The plant growth was significantly inhibited (50%) at 1000 mg/L Pb concentration. Accumulation of Pb was higher in root than in shoot tissues. The maximum level of Pb accumulation was noticed in roots (5.45%) followed by petiole (2.72%) and leaf tissues (0.66%). Increasing the Pb concentration gradually decreased the chlorophyll content. Intracellular distribution of Pb was also studied using SEM-EDX, where the Pb deposition was observed in both root and leaf tissues. MDA content increased in both the leaf and root tissues up to the 400 mg/L Pb treatment and slightly decreased at higher concentrations. The activity of antioxidative enzymes, such as APX and POX, positively correlated with Pb treatment, while in the case of SOD and CAT enzymes increased up to 800 mg/L treatment and then slightly decreased at higher concentration in both leaf and root tissues. Conclusions: These results suggest that water hyacinth plants have efficient mechanism to tolerate Pb toxicity, as evidenced by an increased level of antioxidative enzymes. Results clearly indicate that water hyacinth is a feasible plant for hyperaccumulation of heavy metals from polluted wetlands.