Drought stress is a primary abiotic constraint affecting crop production worldwide. In this study, the role of exogenous spermidine (Spd) in conferring drought-stress-tolerance in maize (Zea mays L.) seedlings was studied by analysing polyamine metabolism and the antioxidant defence system. Two maize cultivars, Xianyu 335 (drought resistant) and Fenghe 1 (drought susceptible), were subjected to drought stress (–0.8 MPa) induced by 15% polyethylene glycol 6000 with or without Spd (0.1 mm) application. Spd significantly reduced the inhibition of plant growth and decreased malondialdehyde and hydrogen peroxide contents and the generation rate of oxidised glutathione caused by drought stress, particularly in Fenghe 1. The activities of superoxide dismutase, ascorbate peroxidase and glutathione reductase further increased with the application of Spd to the stressed plants. Application of Spd significantly moderated the drought-induced reduction in activities of monodehydroascorbate reductase and dehydroascorbate and the ratio ascorbate : dehydroascorbate and reduced the ratio glutathione : oxidised glutathione. With the application of Spd, the contents of Spd and spermine and the activities of arginine decarboxylase, S-adenosyl methionine decarboxylase and diamine oxidase increased significantly in the stressed plants, and the increases were greater in Xianyu 335 than in Fenghe 1. Thus, exogenous Spd successfully reduced oxidative damage by enhancing the antioxidant components, raising the redox state of ascorbate and glutathione, and altering the polyamine pool, which play important roles in improving physiological characteristics and drought stress in maize.