Nutrient management can be an effective approach to enhance plant antioxidant defense system under heavy metal toxicity. A greenhouse experiment was conducted to examine the effects of the two- and three-way interactions of lead (Pb), zinc (Zn) and phosphorus (P) on the activity of catalase (CAT), peroxidase (POD) and superoxide dismutase (SOD) enzymes and the total dry matter (TDM) of rice (Oryza sativa L. cv. Hashemi). This study was conducted as a factorial experiment in completely randomized design with three factors of Zn (0, 25 and 250 mg kg⁻¹), P (0, 50 and 500 mg kg⁻¹) and Pb (0, 200, 400 and 800 mg kg⁻¹) and three replications in calcareous soil. CAT, POD and SOD activity in the fresh leaves and TDM of the rice plant were determined. The effects of two- and three-way interactions of P, Pb and Zn on the antioxidant enzyme activities and TDM of rice plant were significant, and the type of interaction was dependent on the levels of these factors. Soil Pb contamination significantly increased the CAT, POD and SOD enzyme activity but resulted in decreased TDM of the rice plant. Application of 250 mg Zn per kg of soil significantly increased activity of CAT and POD enzymes and TDM at the Pb level of 800 mg kg⁻¹. Phosphorus fertilization significantly increased CAT and POD activity and TDM under Zn- and Pb- contaminated conditions. To increase antioxidant enzyme activity and rice tolerance and growth in Pb-contaminated calcareous soils, combined application of P and Zn at 500 and 250 mg per kg of soil, respectively, can be recommended under similar conditions.