Lettuce (Lactuca sativa L. cv. Romaine) plants were exposed to different levels of urbanization in Jeddah city, Saudi Arabia. They showed different degrees of visible injury symptoms and dramatic changes in enzymatic activities as well as net photosynthetic rates (PN), variable to maximum chlorophyll fluorescence (Fv/Fm) and stomatal conductance (gs). Visual symptoms of phytotoxicity of heavy metals were observed on plants grown at industrial and urban areas, where the concentrations of metals was about 36 times higher than in other sites. The decrease in chlorophyll reached 70 and 64% in plants cultivated in the industrial and urban regions, while lengths of shoots reduced by 50 and 41% in plants collected from the same locations, respectively. The reduction in chlorophyll and other physiological and biochemical parameters were correlated with the concentrations of airborne pollutants measured in the atmosphere of the locations examined. Moreover, lettuce plants cultivated in the industrial region accumulated more heavy metals than others, which can pass into the human food chain. Photosynthetic efficiency was significantly decreased and lipid peroxidation was enhanced. Antioxidant enzymes were significantly altered during exposure. The biochemical and physiological parameters measured in the present study clearly showed that they could form the basis of a plant biomarkers battery for monitoring and predicting early effects of exposure to airborne heavy metals.