Combined effects of ozone (O3) and cadmium (Cd) on growth and physiology of winter wheat (Triticum aestivum L. cv. JM22) were determined. Wheat plants were grown without or with Cd and exposed to charcoal-filtered air (< 10 ppb O3) or elevated O3 (80 ± 5 ppb, 7 hr/day) for 20 days. Results showed that O3 considerably depressed light saturated net photosynthetic rate (-20%), stomatal conductance (-33%), chlorophyll content (-33%), and total biomass (-29%) without Cd. The corresponding decreases were further enhanced by 45%, 56%, 60% and 59%, respectively with Cd, indicating a synergistic effect of O3 and Cd on wheat. Ozone significantly increased the activity of superoxide dismutase (46%), catalase (48%) and peroxidase (56%). However, great increases in malondialdehyde (MDA) content (2.55 folds) and intercellular CO2 concentration (1.13 folds) were noted in O3+Cd treatment compared to control. Our findings demonstrated that the increased anti-oxidative activities in wheat plants exposed to O3+Cd might not be enough to overcome the adverse effects of the combination of both pollutants as evidenced by further increase in MDA content, which is an important indicator of lipid peroxidation. Precise prediction model on O3 damages to crop should be conducted to ensure agricultural production security by considering environmental constraints in an agricultural system in peri-urban regions.